Medicine › Physiology

Erythrocyte Function and Pathophysiology

Works Count: 78723

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Description

This cluster of papers focuses on the role of mechanosensitive ion channels, particularly Piezo1 and Piezo2, in various physiological processes such as mechanotransduction, erythrocyte function, sensory neuron response, and erythropoiesis. It also explores the implications of these channels in diseases related to erythrocytes, sensory perception, and cellular mechanosensation.

Keywords

Piezo1; Piezo2; mechanotransduction; erythrocyte; mechanosensation; ion channels; membrane; sensory neurons; erythropoiesis; apoptosis

[16] Preparation of impermeable ghosts and inside-out vesicles from human erythrocyte membranes

1974-01-01

Theodore L. Steck , Jeffrey A. Kant

Ultraviolet Absorption Spectra of Proteins and Amino Acids

1952-01-01

G. H. Beaven , E. R. Holiday

Hematology: Basic Principles and Practice

1991-08-01

Ronald Hoffman

Part I: Mollecular and Cellular Basis of Hematology. Anatomy and Physiology of the Gene. Protein Synthesis and Intracellular Sorting. Protein Architecture: Relationship of Form and Function. Membrane Biology. Cell Adhesion. … Part I: Mollecular and Cellular Basis of Hematology. Anatomy and Physiology of the Gene. Protein Synthesis and Intracellular Sorting. Protein Architecture: Relationship of Form and Function. Membrane Biology. Cell Adhesion. Cellular Regulatory and Control Mechanism. Part II: Immunologic Basis of Hematology. Overview of the Immune System (including Compartmentalization of the Immune Response). Generation of B-cells. T-cell Immunity. Regulation of Activation of B and T-cells. Tolerance and Autoimmunity. Part III: Biology of Stem Cells and Disorders of Hematopoiesis. Stem Cell Model of Hematopoiesis. Anatomy and Physiology of Hematopoiesis. Growth Factors and the Control of Hematopoiesis. Biology of Erythropoiesis, Erythroid Differentiation and Maturation. Granulopoiesis and Monocytopoiesis. Thrombocytopoiesis. Inherited Forms of Bone Marrow Failure. Aplastic Anemia. Paroxysmal Nocturnal Hemoglobinuria. Pure Red Blood Cell Aplasia. Part IV: Red Blood Cells. Pathobiology of the Red Cell. Approach to the Adult and Child with Anemia. Anemia of Chronic Diseases. Erythrocytosis. Disorders of Iron Metabolism: Iron Deficiency and Overload. Heme Biosynthesis and Its Disorders: Porphyrias and Sideroblastic Anemias. Megaloblastic Anemias. Thalassemia Syndromes. Sickle Cell Disease. Hemoglobin Variants Associated with Hemolytic Anemia, Altered Oxygen Affinity, and Methemoglobinemias. Enzymopathies. Red Cell Membrane Disorders. Autoimmune Hemolytic Anemias. Extrinsic Nonimmune Hemolytic Anemias. Part V: Host Defense and Its Disorders. Immunoglobulins: Structure, Function, and Uses. Complement Biology. Neutrophil Structure and Function. Monocyte and Macrophage Development and Function. Eosinophils and the Hypereosinophilic Syndrome. Disorders of the Phagocyte Function. Disorders of the Lymphocyte Function. Histiocytic Syndromes. Lysosomal Storage Disease. Infectious Mononucleosis and Other Epstein-Barr Virus-Associated Diseases. Spleen and Its Disorders. Systemic Mastocytosis. Part VI: Hemat

A lipid associated with the antiphospholipid syndrome regulates endosome structure and function

1998-03-01

Toshihide Kobayashi , Espen Stang , Karen S. Fang +3 more

Red Cell Metabolism: A Manual of Biochemical Methods.

1971-12-01

E Beutler

Hematology of Infancy and Childhood.

1975-10-01

E. Nathan , Frank A. Oski

History neonatal haematology bone marrow failure disorders of erythrocyte production haemolytic anemias disorders of haemoglobin the phagocyte system the immune system oncology haemostasis genetics supportive theory haematologic manifestations of systemic … History neonatal haematology bone marrow failure disorders of erythrocyte production haemolytic anemias disorders of haemoglobin the phagocyte system the immune system oncology haemostasis genetics supportive theory haematologic manifestations of systemic diseases.

The Diminished Giant Syndrome

1993-03-01

Jagdish N. Bhagwati

Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes).

1987-07-01

Rose M. Johnstone , Mohammed Adam , James R. Hammond +2 more

Vesicles are released during the in vitro culture of sheep reticulocytes which can be harvested by centrifugation at 100,000 X g for 90 min. These vesicles contain a number of … Vesicles are released during the in vitro culture of sheep reticulocytes which can be harvested by centrifugation at 100,000 X g for 90 min. These vesicles contain a number of activities, characteristic of the reticulocyte plasma membrane, which are known to diminish or disappear upon reticulocyte maturation. The activities include acetylcholinesterase, cytochalasin B binding (glucose transporter) nucleoside binding (i.e. nucleoside transporter), Na+-independent amino acid transport, and the transferrin receptor. Enzymes of cytosolic origin are not detectable or are present at low activity in the vesicles. Cultures of whole blood, mature red cells, or white cells do not yield comparable levels of these activities, supporting the conclusion that the activities arise from the reticulocytes. In addition, the lipid composition of the vesicles shows the high sphingomyelin content characteristic of sheep red cell plasma membranes, but not white cell or platelet membranes, also consistent with the conclusion that the vesicles are of reticulocyte origin. It is suggested that vesicle externalization may be a mechanism for shedding of specific membrane functions which are known to diminish during maturation of reticulocytes to erythrocytes.

STUDIES ON LYSOGENESIS I

1951-09-01

G. Bertani

Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1

1995-08-01

Jonathan D. Goldberg , Hsien-Bin Huang , Young‐Guen Kwon +3 more

Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure.

1987-05-01

Brian Seed , A Aruffo

A cDNA encoding the CD2 antigen has been isolated by a highly efficient technique based on transient expression in COS cells and adherence of cells expressing surface antigen to antibody-coated … A cDNA encoding the CD2 antigen has been isolated by a highly efficient technique based on transient expression in COS cells and adherence of cells expressing surface antigen to antibody-coated dishes. COS cells expressing a CD2 cDNA isolated by this method readily formed rosettes with sheep as well as human and other mammalian erythrocytes. Pretreatment of transfected COS cells with anti-CD2 antibody, or pretreatment of human erythrocytes with anti-LFA-3 antibody, abolished rosette formation.

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IMMUNIZATION OF DISSOCIATED SPLEEN CELL CULTURES FROM NORMAL MICE

1967-09-01

Robert I. Mishell , Richard Dutton

A culture system for cell suspensions from mouse spleens has been described. The system provides adequate conditions for in vitro immunization on initial exposure to heterologous erythrocytes. The in vitro … A culture system for cell suspensions from mouse spleens has been described. The system provides adequate conditions for in vitro immunization on initial exposure to heterologous erythrocytes. The in vitro response closely parallels that observed in vivo with respect to size, early kinetics, antigen dose, and the inhibitory effect of passive antibody. The response of cultured cells differs in two respects from that seen in vivo. There is an increase in the ability to discriminate between different varieties of homologous erythrocytes and the in vitro response does not appear to be limited by whatever mechanisms regulate the in vivo response.

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The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy

1973-10-01

Arie J. Verkleij , R.F.A. Zwaal , B. Roelofsen +3 more

Hemoglobin Synthesis in Murine Virus-Induced Leukemic Cells In Vitro: Stimulation of Erythroid Differentiation by Dimethyl Sulfoxide

1971-02-01

Charlotte Friend , William Scher , J. G. Holland +1 more

Cells of a cloned line of murine virus-induced erythroleukemia were stimulated to differentiate along the erythroid pathway by dimethyl sulfoxide at concentrations that did not inhibit growth. A rise in … Cells of a cloned line of murine virus-induced erythroleukemia were stimulated to differentiate along the erythroid pathway by dimethyl sulfoxide at concentrations that did not inhibit growth. A rise in the number of benzidine-positive normoblasts was accompanied by increased synthesis of heme and hemoglobin and a decrease in the malignancy of the cells. This action of dimethyl sulfoxide, which was reversible, may represent the derepression of leukemic cells to permit their maturation.

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Hematopoiesis: A Human Perspective

2012-02-01

Sergei Doulatov , Faiyaz Notta , Elisa Laurenti +1 more

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Piezo1 integration of vascular architecture with physiological force

2014-08-07

Jing Li , Bing Hou , Sarka Tumova +7 more

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Abnormalities in Pericytes on Blood Vessels and Endothelial Sprouts in Tumors

2002-03-01

Shunichi Morikawa , Peter Bałuk , Toshiyuki Kaidoh +3 more

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Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens

1993-10-01

Ana Olivera , Sarah Spiegel

Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels

2010-09-03

Bertrand Coste , Jayanti Mathur , Manuela Schmidt +5 more

Mechanical Responders Identified Although many cells appear to respond to mechanical stimulation through increased conductance of ion channels in the plasma membrane, the actual channels that mediate these effects—which are … Mechanical Responders Identified Although many cells appear to respond to mechanical stimulation through increased conductance of ion channels in the plasma membrane, the actual channels that mediate these effects—which are important in diverse processes from hearing and touch to control of blood pressure—have remained elusive. Coste et al. (p. 55 , published online 2 September) used RNA interference to decrease expression of candidate genes systematically in a mouse neuroblastoma cell line and identified two genes that encode proteins, Piezo1 and Piezo2, which are required for mechanically stimulated cation conductance in these cells and in cultured dorsal root ganglion neurons. Similar proteins are expressed in a range of species from protozoa to vertebrates. The proteins are not similar to known pore-forming proteins and thus could be unusual channels or regulatory components of a channel complex.

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Cytoskeleton—Plasma Membrane Interactions

1992-11-06

Elizabeth J. Luna , Anne L. Hitt

Proteins at the boundary between the cytoskeleton and the plasma membrane control cell shape, delimit specialized membrane domains, and stabilize attachments to other cells and to the substrate. These proteins … Proteins at the boundary between the cytoskeleton and the plasma membrane control cell shape, delimit specialized membrane domains, and stabilize attachments to other cells and to the substrate. These proteins also regulate cell locomotion and cytoplasmic responses to growth factors and other external stimuli. This diversity of cellular functions is matched by the large number of biochemical mechanisms that mediate the connections between membrane proteins and the underlying cytoskeleton, the so-called membrane skeleton. General organizational themes are beginning to emerge from examination of this biochemical diversity.

Red cell membrane: past, present, and future

2008-11-06

Narla Mohandas , Patrick G. Gallagher

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THE ORGANIZATION OF PROTEINS IN THE HUMAN RED BLOOD CELL MEMBRANE

1974-07-01

Theodore L. Steck

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Mechanics of the human red blood cell deformed by optical tweezers

2003-11-01

Ming Dao , Chwee Teck Lim , S. Suresh

Erythropoietin Retards DNA Breakdown and Prevents Programmed Death in Erythroid Progenitor Cells

1990-04-20

Mark J. Koury , Maurice C. Bondurant

The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [3H]thymidine demonstrated DNA cleavage in erythroid progenitor cells that was accompanied by DNA repair … The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [3H]thymidine demonstrated DNA cleavage in erythroid progenitor cells that was accompanied by DNA repair and synthesis. Erythropoietin reduced DNA cleavage by a factor of 2.6. In the absence of erythropoietin, erythroid progenitor cells accumulated DNA cleavage fragments characteristic of those found in programmed cell death (apoptosis) by 2 to 4 hours and began dying by 16 hours. In the presence of erythropoietin, the progenitor cells survived and differentiated into reticulocytes. Thus, apoptosis is a major component of normal erythropoiesis, and erythropoietin controls erythrocyte production by retarding DNA breakdown and preventing apoptosis in erythroid progenitor cells.

Textbook of Endocrinology

1952-03-01

Robert Hardin Williams

what, but the end result is a uniform, informative style. I will not cite figures on how much it has grown since my second edition, other than to say that … what, but the end result is a uniform, informative style. I will not cite figures on how much it has grown since my second edition, other than to say that it weighs more than twice as much, and the increase in content is impressive. The entire field grows ever more complex. As one old-timer remarked a number of years ago, Blood clotted a lot easier in the old To that I would add that blood did everything a lot easier in the old days. To squeeze all of this into a man¬ ageable volume, the publisher has gone to a smaller type size than before, smaller than usual in medical texts. This is not really objection¬ able—I found it easy to read. This type size does allow an increase in content of about 40% per page. When compared with the immedi¬ ately preceding edition, this volume includes some newly described condi¬ tions (hereditary pyropoikilocytosis; McLeod phenotype), new ways of looking at old problems (FrenchAmerican-British group classification of acute leukemias), and the latest thoughts of chemotherapeutic combi¬ nations in leukemia (TAD, TRAP, OAP, and POMP). I recommend Wintrobe's Clinical Hematology without reservation to all with an interest in clinical or experi¬ mental hematology.

Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis

1990-01-01

Gwyn T. Williams , Christopher A. Smith , Elaine Spooncer +2 more

Programmed Anuclear Cell Death Delimits Platelet Life Span

2007-03-01

Kylie D. Mason , Marina R. Carpinelli , Jamie I. Fletcher +7 more

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Role of CD47 as a Marker of Self on Red Blood Cells

2000-06-16

Per‐Arne Oldenborg , Alex Zheleznyak , Yifu Fang +3 more

The immune system recognizes invaders as foreign because they express determinants that are absent on host cells or because they lack “markers of self” that are normally present. Here we … The immune system recognizes invaders as foreign because they express determinants that are absent on host cells or because they lack “markers of self” that are normally present. Here we show that CD47 (integrin-associated protein) functions as a marker of self on murine red blood cells. Red blood cells that lacked CD47 were rapidly cleared from the bloodstream by splenic red pulp macrophages. CD47 on normal red blood cells prevented this elimination by binding to the inhibitory receptor signal regulatory protein alpha (SIRPα). Thus, macrophages may use a number of nonspecific activating receptors and rely on the presence or absence of CD47 to distinguish self from foreign. CD47-SIRPα may represent a potential pathway for the control of hemolytic anemia.

Essential role for Nix in autophagic maturation of erythroid cells

2008-05-04

Héctor Sandoval , Perumal Thiagarajan , Swapan K. Dasgupta +4 more

Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria

2004-12-06

S. Suresh , Joachim P. Spatz , John Mills +5 more

The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes

1963-01-01

James T. Dodge , Carolyn D. Mitchell , Donald J. Hanahan

Appearance of Water Channels in Xenopus Oocytes Expressing Red Cell CHIP28 Protein

1992-04-17

Gregory M. Preston , Tiziana Piazza Carroll , William B. Guggino +1 more

Water rapidly crosses the plasma membrane of red blood cells (RBCs) and renal tubules through specialized channels. Although selective for water, the molecular structure of these channels is unknown. The … Water rapidly crosses the plasma membrane of red blood cells (RBCs) and renal tubules through specialized channels. Although selective for water, the molecular structure of these channels is unknown. The CHIP28 protein is an abundant integral membrane protein in mammalian RBCs and renal proximal tubules and belongs to a family of membrane proteins with unknown functions. Oocytes from Xenopus laevis microinjected with in vitro-transcribed CHIP28 RNA exhibited increased osmotic water permeability; this was reversibly inhibited by mercuric chloride, a known inhibitor of water channels. Therefore it is likely that CHIP28 is a functional unit of membrane water channels.

A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes

1995-11-01

Philipp E. Scherer , Suzanne Williams , M Fogliano +2 more

We describe a novel 30-kDa secretory protein, Acrp30 (adipocyte complement-related protein of 30 kDa), that is made exclusively in adipocytes and whose mRNA is induced over 100-fold during adipocyte differentiation. … We describe a novel 30-kDa secretory protein, Acrp30 (adipocyte complement-related protein of 30 kDa), that is made exclusively in adipocytes and whose mRNA is induced over 100-fold during adipocyte differentiation. Acrp30 is structurally similar to complement factor C1q and to a hibernation-specific protein isolated from the plasma of Siberian chipmunks; it forms large homo-oligomers that undergo a series of post-translational modifications. Like adipsin, secretion of Acrp30 is enhanced by insulin, and Acrp30 is an abundant serum protein. Acrp30 may be a factor that participates in the delicately balanced system of energy homeostasis involving food intake and carbohydrate and lipid catabolism. Our experiments also further corroborate the existence of an insulin-regulated secretory pathway in adipocytes. We describe a novel 30-kDa secretory protein, Acrp30 (adipocyte complement-related protein of 30 kDa), that is made exclusively in adipocytes and whose mRNA is induced over 100-fold during adipocyte differentiation. Acrp30 is structurally similar to complement factor C1q and to a hibernation-specific protein isolated from the plasma of Siberian chipmunks; it forms large homo-oligomers that undergo a series of post-translational modifications. Like adipsin, secretion of Acrp30 is enhanced by insulin, and Acrp30 is an abundant serum protein. Acrp30 may be a factor that participates in the delicately balanced system of energy homeostasis involving food intake and carbohydrate and lipid catabolism. Our experiments also further corroborate the existence of an insulin-regulated secretory pathway in adipocytes.

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The minimum energy of bending as a possible explanation of the biconcave shape of the human red blood cell

1970-01-01

Peter B. Canham

The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells

1989-05-01

D Metcalf

Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane

1971-06-01

Grant Fairbanks , Theodore L. Steck , Donald F. H. Wallach

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrophoretic analysis of the major polypeptides of the human erythrocyte membraneG. Fairbanks, Theodore L. Steck, and D. F. H. WallachCite this: Biochemistry 1971, 10, 13, 2606–2617Publication Date … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrophoretic analysis of the major polypeptides of the human erythrocyte membraneG. Fairbanks, Theodore L. Steck, and D. F. H. WallachCite this: Biochemistry 1971, 10, 13, 2606–2617Publication Date (Print):June 1, 1971Publication History Published online1 May 2002Published inissue 1 June 1971https://pubs.acs.org/doi/10.1021/bi00789a030https://doi.org/10.1021/bi00789a030research-articleACS PublicationsRequest reuse permissionsArticle Views4517Altmetric-Citations6745LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Piezo2 is the major transducer of mechanical forces for touch sensation in mice

2014-12-01

Sanjeev S. Ranade , Seung-Hyun Woo , Adrienne E. Dubin +7 more

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A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis

1991-05-01

Michael L. Mucenski , Kersten McLain , Ann B. Kier +6 more

Identification of Two Distinct Mechanisms of Phagocytosis Controlled by Different Rho GTPases

1998-11-27

Emmanuelle Caron , Alan Hall

The complement and immunoglobulin receptors are the major phagocytic receptors involved during infection. However, only immunoglobulin-dependent uptake results in a respiratory burst and an inflammatory response in macrophages. Rho guanosine … The complement and immunoglobulin receptors are the major phagocytic receptors involved during infection. However, only immunoglobulin-dependent uptake results in a respiratory burst and an inflammatory response in macrophages. Rho guanosine triphosphatases (molecular switches that control the organization of the actin cytoskeleton) were found to be essential for both types of phagocytosis. Two distinct mechanisms of phagocytosis were identified: Type I, used by the immunoglobulin receptor, is mediated by Cdc42 and Rac, and type II, used by the complement receptor, is mediated by Rho. These results suggest a molecular basis for the different biological consequences that are associated with phagocytosis.

Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis

1992-09-01

Eva Y.-H.P. Lee , Chi-Yao Chang , Nanpin Hu +5 more

Mutation of the mouse klotho gene leads to a syndrome resembling ageing

1997-11-06

Makoto Kuro‐o , Yutaka Matsumura , Hiroki Aizawa +7 more

Spectrin and Ankyrin-Based Pathways: Metazoan Inventions for Integrating Cells Into Tissues

2001-07-01

Vann Bennett , Anthony J. Baines

The spectrin-based membrane skeleton of the humble mammalian erythrocyte has provided biologists with a set of interacting proteins with diverse roles in organization and survival of cells in metazoan organisms. … The spectrin-based membrane skeleton of the humble mammalian erythrocyte has provided biologists with a set of interacting proteins with diverse roles in organization and survival of cells in metazoan organisms. This review deals with the molecular physiology of spectrin, ankyrin, which links spectrin to the anion exchanger, and two spectrin-associated proteins that promote spectrin interactions with actin: adducin and protein 4.1. The lack of essential functions for these proteins in generic cells grown in culture and the absence of their genes in the yeast genome have, until recently, limited advances in understanding their roles outside of erythrocytes. However, completion of the genomes of simple metazoans and application of homologous recombination in mice now are providing the first glimpses of the full scope of physiological roles for spectrin, ankyrin, and their associated proteins. These functions now include targeting of ion channels and cell adhesion molecules to specialized compartments within the plasma membrane and endoplasmic reticulum of striated muscle and the nervous system, mechanical stabilization at the tissue level based on transcellular protein assemblies, participation in epithelial morphogenesis, and orientation of mitotic spindles in asymmetric cell divisions. These studies, in addition to stretching the erythrocyte paradigm beyond recognition, also are revealing novel cellular pathways essential for metazoan life. Examples are ankyrin-dependent targeting of proteins to excitable membrane domains in the plasma membrane and the Ca 2+ homeostasis compartment of the endoplasmic reticulum. Exciting questions for the future relate to the molecular basis for these pathways and their roles in a clinical context, either as the basis for disease or more positively as therapeutic targets.

Atomic structure of the actin: DNase I complex

1990-09-01

Wolfgang Kabsch , Hans Georg Mannherz , Dietrich Suck +2 more

Erythroid colony formation in cultures of mouse and human bone marrow: Analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose‐concanavalin A

1974-04-01

Norman N. Iscove , Fritz Sieber , Kaspar H. Winterhalter

Abstract Assay of red cell progenitors by colony formation in culture is expected to allow study of early events in erythroid differentiation in animal models and in man. In this … Abstract Assay of red cell progenitors by colony formation in culture is expected to allow study of early events in erythroid differentiation in animal models and in man. In this communication, a simplification of the culture method for mouse bone marrow cells originally reported by Stephenson et al. ('71) is described. In the modified procedure, plasma clot is replaced by methyl cellulose, and scoring of erythroid colonies is done directly in the plates without staining. With additional modification the system proved applicable to the culture of erythroid colonies from human bone marrow as well. The development of both mouse and human erythroid colonies was dependent on “erythroid colony stimulating activity” (E‐CSA) supplied by extracts of anemic sheep plasma, or by extracts of urine from anemic patients. Over a certain range, the number of colonies was a function of dose of E‐CSA. In addition to E‐CSA, these extracts also possessed erythropoietin activity as measured in plethoric mice. The possible chemical equivalence of urinary E‐CSA and erythropoietin was suggested by their similar behavior on both gel filtration and affinity chromatography on agarose‐concanavalin A. The finding further suggests that the culture method might prove useful for the bioassay of erythropoietin. Granulocyte colony stimulating activity (G‐CSA) was also present in the urine extracts, as detected in cultures of mouse bone marrow. Virtually all of this activity was bound on agarose‐con A, whereas only a small fraction of E‐CSA was retained on this material. Agarose‐con A may thus be useful for the purification of erythropoietin.

Metabolic dependence of red cell deformability

1969-05-01

Robert I. Weed , Paul L. LaCelle , Edward W. Merrill

The contribution of the metabolic state of human erythrocytes to maintenance of cellular deformability was studied during and after in vitro incubation in serum for periods up to 28 hr. … The contribution of the metabolic state of human erythrocytes to maintenance of cellular deformability was studied during and after in vitro incubation in serum for periods up to 28 hr. An initial loss of membrane deformability became apparent between 4 and 6 hr when cellular adenosine triphosphate (ATP) levels were approximately 70% of initial values. Membrane deformability then remained stable between 6 and 10 hr. After 10 hr, when cellular ATP had decreased to < 15% of initial values, progressive parallel changes occurred in red cell calcium which increased 400% by 24 hr and in the viscosity of red cell suspensions which had risen 500-750% at 24 hr. A further progressive decrease in membrane deformability also occurred and was reflected by a 1000% increase in negative pressure required to deform the membrane. Red cell filterability decreased to zero as the disc-sphere shape transformation ensued. These changes were accompanied by an increase in ghost residual hemoglobin and nonhemoglobin protein. Regeneration of ATP in depleted cells by incubation with adenosine produced significant reversal of these changes, even in the presence of ouabain. Introduction of calcium into reconstituted ghosts prepared from fresh red cells mimicked the depleted state, and introduction of ATP, ethylenediamine tetraacetate (EDTA), and magnesium into depleted cells mimicked the adenosine effects in intact depleted cells. ATP added externally to 24-hr depleted cells was without effect. Simultaneous introduction of EDTA, ATP, or magnesium along with calcium into reconstituted ghosts prevented the marked decrease in deformability produced by calcium alone. Incorporation of adenosine diphosphate (ADP), nicotinamide adenine dinucleotide (NAD), NAD phosphate (NADP), NADP, reduced form (NADPH), glutatione, reduced form (GSH), inosine triphosphate (ITP), guanosine triphosphate (GTP), and uridine triphosphate (UTP) was without effect. These data suggest that a major role of ATP in maintenance of red cell viability relates to preservation of red cell membrane deformability. It is proposed that the changes seen in the physical properties of ATP-depleted erythrocytes represent ATP-calcium-dependent sol-gel changes occurring at the interface between the membrane and the cell interior, and that the sol-gel balance determines membrane deformability.

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Establishment and characterization of a unique human cell line that proliferates dependently on GM‐CSF, IL‐3, or erythropoietin

1989-08-01

Toshio Kitamura , Tsuyoshi Tange , Takashi Terasawa +7 more

Abstract We have established a novel cell line, designated as TF‐1, from a patient with erythroleukemia, which showed complete growth dependency on granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or on interleukin‐3 (IL‐3) … Abstract We have established a novel cell line, designated as TF‐1, from a patient with erythroleukemia, which showed complete growth dependency on granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or on interleukin‐3 (IL‐3) and carried a homogeneous chromosomal abnormality (54X). Erythropoietin (EPO) also sustained the short‐term growth of TF‐1, but did not induce erythroid differentiation. These three hematopoietic growth factors acted on TF‐1 synergistically. Transforming growth factorβ and interferons inhibited the factor‐dependent growth of TF‐1 cells in a dose‐dependent fashion, and monocyte‐colony stimulating factor and interkeukin‐1 enhanced the GM‐CSF‐dependent growth of TF‐1. Ultrastructural studies revealed some very immature features in this cell line. Although TF‐1 cells do not express glycophorin A or carbonyl anhydrase I, the morphological and cytochemical features, and the constitutive expression of globin genes, indicate the commitment of TF‐1 to erythroid lineage. When induced to differentiate, TF‐1 entered two different pathways. Specifically, hemin and delta‐arninolevulinic acid induced hemoglobin synthesis, whereas TPA induced dramatic differentiation of TF‐1 into macrophage‐like cells. In summary, TF‐1 is a cell lineof immature erythroid origin that requires GM‐CSF, IL‐3, or EPO for its growth and that has the ability to undergo differentiation into either more mature erythroid cells or into macrophage‐like cells. TF‐1 is auseful tool for analyzing the human receptors for IL‐3, GM‐CSF, and EPO or the signal transduction of these hemopoietic growth factors.

Piezo proteins are pore-forming subunits of mechanically activated channels

2012-02-17

Bertrand Coste , Bailong Xiao , Jose S. Santos +7 more

Treatment of Persistent Gross Hematuria with Tranexamic Acid in Autosomal Dominant Polycystic Kidney Disease

2017-01-01

Qing Yao , Ming Wu , Jie Zhou +7 more

Snakes' venom is a mixture of biologically active substances, containing proteins and peptides. A number of these proteins interact with haemostasis system components. Activators and inhibitors affecting blood coagulation and … Snakes' venom is a mixture of biologically active substances, containing proteins and peptides. A number of these proteins interact with haemostasis system components. Activators and inhibitors affecting blood coagulation and fibrinolysis systems are of special interest. Venom components can be classified into three main groups, such as procoagulants, anticoagulants and fibrinolytic enzymes according to their action. This review is focused on enzymes from Agkistrodon halys halys venom. They are thrombine-like enzyme, named Ancystron-H, flbrinogenolytic enzyme, protein C activator and platelet aggregation inhibitor. Ancystron-H is used for determination of fibrinogen level in blood plasma of patients undergoing heparin treatment and blood coagulation inhibitors accumulation. The fibrinogenolytic enzyme can be used as the instrument for protein-protein interactions in fibrinogen-fibrin system. The protein C activator is used for protein C level determination in blood plasma with different pathologies. Functions of the platelet aggregation inhibitor, belonging to disintegrins group, can be used for development of antithrombotic preparations. Information about the use of snake venoms in science and medicine is presented.

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Red Cell Metabolism. A Manual of Biochemical Methods.

1975-12-01

Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g.

1968-01-01

Arne Bøyum

Red Blood Cells and their Immunoregulatory Role

2025-06-25

Angela Risso , Guglielmo Antonutto | Medical Principles and Practice

The physiological roles played by red blood cells (RBCs), i.e. oxygen transport to all cells and tissues, CO2 delivery to the lungs, control of pH in blood and ions transport … The physiological roles played by red blood cells (RBCs), i.e. oxygen transport to all cells and tissues, CO2 delivery to the lungs, control of pH in blood and ions transport into and out of the cell membrane, have been investigated extensively over the past decades. The roles mature and immature RBCs play, while in the blood vessels, when they come in contact with other blood and endothelial cells, are only partially known. Here we will focus on the RBCs ability to modulate innate and adaptive immune responses when they interact with cells or molecules encountered during their flow in the vessels. We will outline the possible clinical impact on treatment of some diseases, such as autoimmune diseases, inflammatory pathologies or tumors, where immunotherapy can be applied.

Mutualist-pathogen co-colonisation modulates phosphoinositide signatures at host intracellular interfaces

2025-06-24

Alex Guyon , Theresa Staps , Lyne Badot +1 more

SUMMARY The host membrane that surrounds intracellular microbes forms a critical interface influencing whether interactions result in mutualism or pathogenesis. While phosphoinositide identities differ between pathogen and mutualist interface membranes, … SUMMARY The host membrane that surrounds intracellular microbes forms a critical interface influencing whether interactions result in mutualism or pathogenesis. While phosphoinositide identities differ between pathogen and mutualist interface membranes, it is unclear if these are modulated during co-colonisation. To address this, we generated Nicotiana benthamiana plants expressing biosensors for PI4P and PI(4,5)P 2 and imaged root colonisation by the pathogenic oomycete Phytophthora palmivora and the mutualistic fungus Funneliformis mosseae . Binary host-microbe interactions revealed distinct patterns: PI(4,5)P 2 was tip-enriched at mutualist structures but evenly distributed around pathogen structures, while PI4P was absent from pathogen-associated membranes but present at mutualist interfaces. Strikingly, co-colonisation altered host membrane identity, triggering PI4P recruitment at pathogen haustoria, and enhanced resistance to P. palmivora . These findings reveal that phosphoinositide signatures distinguish pathogenic and mutualistic interfaces and are dynamically remodelled during co-colonisation, likely influencing interaction outcomes. Abstract Figure

Piezo1 Modulates Synovial Macrophage Polarization and Function to Influence the Progression of Temporomandibular Joint Osteoarthritis

2025-06-24

Lisong Shen | International Journal of Oral and Maxillofacial Surgery

Red Cell Death in Renal Disease: The Role of Eryptosis in CKD and Dialysis Patients

2025-06-24

Grazia Maria Virzì , Anna Clementi , Claudio Ronco +1 more | Cells

Eryptosis is a programmed cellular death involving red blood cells (RBCs). It is a physiological mechanism that leads to the removal of defective erythrocytes, similarly to apoptosis. Its typical features … Eryptosis is a programmed cellular death involving red blood cells (RBCs). It is a physiological mechanism that leads to the removal of defective erythrocytes, similarly to apoptosis. Its typical features are cell shrinkage, cell membrane blebbing, and membrane scrambling with the consequent exposure of the aminophospholipid phosphatidylserine on the outer surface of RBCs. Different mechanisms play a role in the pathogenesis of eryptosis, such as the increase in cytosolic calcium concentration, oxidative stress, inflammation, and uremic toxins. If erythrocyte synthesis does not compensate for the accelerated eryptosis, anemia may develop. Moreover, enhanced eryptosis contributes to the pathogenesis of different clinical diseases, such as diabetes, sepsis, metabolic syndrome, and uremia. In particular, in patients with chronic kidney disease (CKD), deficiencies of erythropoietin and iron may further reduce the lifespan of RBCs. In this review, we focused on eryptosis in CKD and end-stage renal disease on peritoneal dialysis (PD) and hemodialysis (HD).

Red Blood Cell Membrane Lipidomics: Potential Biomarkers Detecting Method for Plasma Volume Overload and Major Adverse Cardiovascular Events in Chronic Heart Failure Patients

2025-06-23

Lin Zhang , Xiangqin Ou , Jingyi Lin +7 more | Advanced Science

Plasma volume fluctuations limit the utility of circulating lipidomics in chronic heart failure (CHF). In contrast, red blood cell (RBC) membrane lipidomics may serve as stable biomarkers that are unaffected … Plasma volume fluctuations limit the utility of circulating lipidomics in chronic heart failure (CHF). In contrast, red blood cell (RBC) membrane lipidomics may serve as stable biomarkers that are unaffected by plasma volume changes. Two cohorts are included to investigate the association between RBC indicators and CHF. RBC membrane lipidomics is first used to characterize CHF and its impact on plasma volume overload (PVO) and major adverse cardiovascular events (MACE). The first cohort (n = 507,638) shows that the erythrocyte stress index (ESI), better than traditional RBC indicators, is associated with the prevalence of CHF with odds ratio (OR) and confidence interval (CI) of 1.57 (95% CI,1.55-1.59). ESI is also linked with in-hospital death in CHF. Another cohort (n = 1,550) indicated RBC membrane lipidomics ceramide subtype Cer 18:0;O2/16:0 and lysophosphatidylethanolamine subtype LPE 18:0 has an AUC of PVO with 0.75 and 0.61. The above two lipids are risk factors of PVO with OR of 1.62 (95% CI, 1.47-1.80) and 1.11 (95% CI, 1.06-1.16). They also are risk factors for MACE, with hazard ratios (HR) of 1.04 (95% CI, 1.01-1.07) and 1.06 (95% CI, 1.01-1.10). This research emphasizes the potential value of RBC membrane lipidomics for CHF development, prognosis, and treatment.

Novel SPTB Variations Cause Hereditary Spherocytosis With Cholangiolithiasis and Severe Intrahepatic Cholestasis

2025-06-23

Linlin Li , Sadik Ali , Qiong Bin | Annals of Human Genetics

Hereditary spherocytosis (HS) is a chronic non-immune hemolytic anemia caused by congenital defects in the erythrocyte membrane. Gene variations can lead to HS, and the SPTB gene variation is one … Hereditary spherocytosis (HS) is a chronic non-immune hemolytic anemia caused by congenital defects in the erythrocyte membrane. Gene variations can lead to HS, and the SPTB gene variation is one of them. However, HS with cholangiolithiasis and extremely intrahepatic cholestasis had been rarely discussed as a phenotype caused by SPTB gene variation, and the pathogenic mechanism of this gene variation is still unclear. Clinical data were collected, genetic analysis was carried out by high throughput sequencing and Sanger sequencing, and then pathogenic mechanism of gene variation was revealed by Western blot analysis. Two children were admitted because of severe jaundice and finally confirmed as HS complicated with cholangiolithiasis and severe intrahepatic cholestasis. After conservative treatments, symptoms of cholangiolithiasis and intrahepatic cholestasis relieved. Respectively, two novel heterozygous variations of SPTB gene, (NM_001024858.4: c.493_494insTG, p. Q165fs) and (NM_001024858.4: c.1715delT, p. L572X), were identified in these two families. Western blot analysis revealed that these two pathogenic variations all cause decreased protein expression of β-spectrin. We have identified two novel SPTB variations in HS with cholangiolithiasis and intrahepatic cholestasis. Moreover, our study enhances current understanding of the phenotype and molecular mechanisms associated with SPTB variation.

Apical size reduction by macropinocytosis alleviates tissue crowding

2025-06-23

Enzo Bresteau , Eve E Suva , Christopher Revell +7 more | Nature Communications

Investigating the binding strength between subtypes red blood cells and their corresponding antibodies and rapidly differentiating subtypes in a microchannel

2025-06-23

Ding‐Ping Chen , Yi‐Ping Ho , Hsieh‐Fu Tsai +3 more | Microfluidics and Nanofluidics

Drie gezichten van pediatrische sferocytose: een retrospectieve casusreeks uit een regionaal ziekenhuis

2025-06-23

Alexander Dereu , Johan Hellinckx , Veerle Mondelaers | Tijdschrift voor Geneeskunde

Three faces of pediatric spherocytosis: a retrospective case series from a regional hospital Hereditary spherocytosis is one of the most prevalent forms of inherited chronic hemolysis worldwide. Specifically in the … Three faces of pediatric spherocytosis: a retrospective case series from a regional hospital Hereditary spherocytosis is one of the most prevalent forms of inherited chronic hemolysis worldwide. Specifically in the Caucasian population, it is the most prevalent form. Intrinsic defects in erythrocyte membrane proteins lead to spherical erythrocytes with reduced deformability and, consequently, a shortened lifespan. The destruction of these spherocytes results in anemia, jaundice and bilirubin-containing lithiasis or pigment stones. It is a genetically heterogeneous disease, leading to a wide spectrum of phenotypes, ranging from mild forms with compensated hemolysis to severe forms of life-threatening anemia, often requiring frequent transfusions. Typically, sferocytosis presents as neonatal jaundice or as an hemolytic crisis triggered by a provoking factor such as a Parvovirus B19. A Parvovirus B19 infection can temporarily suppress erythropoiesis, which together with hemolysis leads to profound anemia (aplastic crisis). Depending on the severity of the disease, treatment can range from a one-time or intermittent blood transfusion to splenectomy and/or cholecystectomy. Due to the significantly increased risk of post-splenectomy sepsis, the decision for splenectomy must be carefully considered. The aim of this article is to provide an overview of the characteristics, clinical presentation and therapeutic options for spherocytosis in a pediatric population. Retrospective data on 15 spherocytosis patients will be compared with current literature. This case series was collected within the pediatric department of AZ Klina hospital.

Прогностическая значимость фукозы крови как предиктора гепатоцеллюлярной карциномы у пациентов с циррозом печени в исходе хронического гепатита С

2025-06-20

Ю. В. Юркевич , Л.А. Анисько | Клиническая инфектология и паразитология

Цель. Оценить прогностическую значимость фукозы крови как предиктора гепатоцеллюлярной карциномы у пациентов с циррозом печени в исходе хронического гепатита С. Материалы и методы. В исследование включены 44 пациента с циррозом … Цель. Оценить прогностическую значимость фукозы крови как предиктора гепатоцеллюлярной карциномы у пациентов с циррозом печени в исходе хронического гепатита С. Материалы и методы. В исследование включены 44 пациента с циррозом печени в исходе хронического гепатита С, в том числе 10/44 (23%) пациентов с верифицированной гепатоцеллюлярной карциномой. Пациентам выполнялось исследование содержания фукозы крови и неспецифической фракции альфа-фетопротеина. Оценка прогностической значимости предикторов гепатоцеллюлярной карциномы осуществлялась с помощью ROC-анализа с оценкой чувствительности, специфичности, площади под кривой, для которых методом бутстрэпа вычислялись 95% доверительные интервалы. Статистическая значимость различий между площадями под кривыми для фукозы и альфа-фетопротеина оценивалась с применением двустороннего бутстрэп-теста. Различия считались статистически значимыми при p<0,05. Статистический анализ выполнен в R-версии 4.4.1 с использованием библиотек table1, pROC. Результаты. Медиана содержания фукозы крови у пациентов с циррозом печени без гепатоцеллюлярной карциномы составила 17,8 (14,2; 20,5) мг/100 мл, у пациентов с циррозом печени и гепатоцеллюлярной карциномой – 22,9 (20,8; 25,3) мг/100 мл. По результатам ROC-анализа, площадь под кривой для фукозы как предиктора гепатоцеллюлярной карциномы у пациентов с циррозом печени в исходе хронического гепатита С составила 85,3% (95% ДИ 74,1–96,5%). Оптимальным значением содержания фукозы крови являлось 19,5 мг/100 мл с чувствительностью 100% (95% ДИ 100–100%) и специфичностью 71% (95% ДИ 55–85%). При сравнении ROC-кривых с применением бутстрэп-теста выявлены статистически значимые различия между площадью под кривыми фукозы крови и альфа-фетопротеина (p=0,01). Заключение. Фукоза крови является высокочувствительным предиктором гепатоцеллюлярной карциномы у пациентов с циррозом печени в исходе хронического гепатита С. Purpose. To evaluate the prognostic value of blood fucose as a predictor of hepatocellular carcinoma in patients with HCV-associated liver cirrhosis. Materials and methods. The study included 44 patients with HCV-associated liver cirrhosis. Hepatocellular carcinoma was confirmed in 10/44 (23%) patients. Blood fucose levels and nonspecific alpha-fetoprotein fraction were measured in all patients. Diagnostic characteristics of fucose and alpha-fetoprotein were assessed using ROC analysis, with evaluation of sensitivity, specificity, and area under the curve. Confidence intervals (95% CI) were calculated using the bootstrap method. Area under the curves for fucose and alpha-fetoprotein were compared with two-sided bootstrap test. Differences were considered statistically significant at p <0.05. Statistical analysis was performed in R version 4.4.1 with libraries table1 and pROC. Results. In patients with liver cirrhosis without hepatocellular carcinoma, median fucose concentration was 17.8 (14.2; 20.5) mg/100 mL. In patients with cirrhosis and hepatocellular carcinoma median fucose concentration was 22.9 (20.8; 25.3) mg/100 mL. According to the ROC analysis, area under the curve for blood fucose was 85.3% (95% CI 74.1–96.5%). The optimal fucose cutoff value was 19.5 mg/100 mL with a sensitivity of 100% (95% CI 100–100%) and specificity of 71% (95% CI 55–85%). Bootstrap test demonstrated a statistically significant difference between the area under the curves for blood fucose and alpha-fetoprotein (p=0.01). Conclusion. Blood fucose is a highly sensitive predictor of hepatocellular carcinoma in patients with HCV-associated liver cirrhosis.

Red Blood Cells Are Critical for Hemostasis and Thrombosis

2025-06-20

Hyun Jung Kim , Katie Houck , Sam Joy Neuffer +1 more | Seminars in Thrombosis and Hemostasis

Hemostasis in humans has traditionally been considered to a function of platelets, coagulation, and the subendothelial matrix, but the role of red blood cells (RBCs) has been increasingly recognized. RBCs … Hemostasis in humans has traditionally been considered to a function of platelets, coagulation, and the subendothelial matrix, but the role of red blood cells (RBCs) has been increasingly recognized. RBCs regulate hemostasis through biophysical and biochemical means. For the former, faster-moving RBCs in the center of vessels marginalize platelets and plasma to the vessel walls, where the platelets constantly probe the endothelial surface for injury. RBC counts also determine blood viscosity, which regulates the shear stress of laminar blood flow. For the latter, RBCs are the largest pool of adenosine triphosphate, which, upon release, is rapidly hydrolyzed to adenosine diphosphate. Both ATP and ADP activate platelets. Quantitative and qualitative abnormalities in RBCs have also been consistently identified as significant risk factor for arterial and venous thrombosis. Thrombosis is a major complication associated with diseases such as polycythemia vera, secondary erythrocytosis, and sickle cell anemia, all of which present with changes in numbers and physical properties of RBCs. Thrombosis is also common in conditions with significant hemolysis, such as paroxysmal nocturnal hemoglobinuria, severe infections, and when patients are on mechanical support. In this review, we discuss findings from clinical observations and mechanistic studies of how RBCs regulate hemostasis and contribute to thrombosis.

Piezo1 selectively enhances TGF-β1-induced IgA class switching by B cells

2025-06-19

Yoonji Jung , Young Hwan Han , Jaeku Kang +2 more | Cellular and Molecular Life Sciences

Piezo1 is a mechanosensitive cationic channel that regulates Ca2+ influx, gene transcription, and cell migration. Recent studies suggest that Piezo1 affects regulatory T cells differentiation and is critical in B … Piezo1 is a mechanosensitive cationic channel that regulates Ca2+ influx, gene transcription, and cell migration. Recent studies suggest that Piezo1 affects regulatory T cells differentiation and is critical in B cell responses to membrane-presented antigens. However, the role of Piezo1 in B cells function is not completely elucidated. This study investigated the role of Piezo1 in IgA class switching and Ab production by mouse B cells using qRT-PCR, flow cytometric analysis, and isotype-specific ELISA. The Piezo1 agonist Yoda1 selectively upregulated TGF-β1-induced germline α transcripts (GLTα) /post-switch α transcripts (GLTα) expression, surface IgA expression, and IgA production. Conversely, the Piezo1 inhibitor OB-1 reduced IgA class switching. TGF-β1-induced IgA class switching and IgA production decreased in Piezo1 knockdown B cells. Additionally, Piezo1 enhanced TGF-β1-induced Smad3 phosphorylation. These results demonstrate that Piezo1 selectively enhances TGF-β1-induced IgA class switching via Smad3 phosphorylation, leading to IgA production in B cells.

Uncovering Glucose-6-Phosphate Isomerase (GPI) Deficiency in a Five-Year-Old With Hemolytic Anemia in Bahrain

2025-06-19

Maryam Y Busehail , Faieza Qasim , Fatema J Alasheeri +1 more | Cureus

Ankyrin-G and Its Binding Partners in Neurons: Orchestrating the Molecular Structure of the Axon Initial Segment

2025-06-19

Xiaohua Zhu , Yan-yan Yu , Zikang Jiang +2 more | Biomolecules

The axon initial segment (AIS) is a specialized subcellular domain that plays an essential role in action potential initiation and the diffusion barrier. A key organizer of the AIS is … The axon initial segment (AIS) is a specialized subcellular domain that plays an essential role in action potential initiation and the diffusion barrier. A key organizer of the AIS is Ankyrin-G, a scaffolding protein responsible for clustering voltage-gated ion channels, cell adhesion molecules (CAMs), and cytoskeletal components at this critical neuronal domain. Recent proteomic analyses have revealed a complex network of proteins in the AIS, emphasizing Ankyrin-G's central role in its molecular architecture. This review discusses new findings in the study of AIS-associated proteins. It explains how Ankyrin-G and its binding partners (such as ion channels, CAMs, spectrins, actin, and microtubule-associated proteins including end-binding protein 3, tripartite motif-containing protein 46, and calmodulin-regulated spectrin-associated protein 2) organize their structure. Understanding the dynamic regulation and molecular interactions within the AIS offers insights into neuronal excitability and reveals potential therapeutic targets for axonal dysfunction-related diseases. Through these dynamic interactions, Ankyrin-G ensures the proper alignment and dense clustering of key channel complexes, thereby maintaining the AIS's distinctive molecular and functional identity. By further unraveling the complexity of Ankyrin-G's interactome, our understanding of AIS formation, maintenance, and plasticity will be considerably enhanced, contributing to the elucidation of the pathogenesis of neurological and neuropsychiatric disorders.

Hereditary Elliptocytosis Resulting From Heterozygosity for β Spectrin Tandil

2025-06-18

María Angustias Molina Arrebola , Barbara J. Bain | American Journal of Hematology

Characterizing Traction Forces in Upstream-Migrating Hematopoietic-like KG1a Cells Under Shear Flow

2025-06-17

Dong-hun Lee , Daniel A. Hammer | bioRxiv (Cold Spring Harbor Laboratory)

Cell migration is critical to leukocyte function, enabling leukocytes to patrol tissues and respond to inflammatory cues. Upstream migration is a distinct form of cell motility which enables leukocytes to … Cell migration is critical to leukocyte function, enabling leukocytes to patrol tissues and respond to inflammatory cues. Upstream migration is a distinct form of cell motility which enables leukocytes to move against the direction of fluid flow on Intercellular Adhesion Molecule-1 (ICAM-1) surfaces. Upstream migration is mediated by the leukocyte integrin, Lymphocyte Function-Associated Antigen-1 (LFA-1). While this behavior has been observed across multiple immune cell types, the mechanical forces underlying upstream migration have not been measured. Here, we demonstrate the use of Traction Force Microscopy (TFM) to quantify spatiotemporal patterns of force generation during upstream migration of KG1a cells, a hematopoietic progenitor cell line that exhibits robust upstream migration on ICAM-1 functionalized hydrogels. Under static (no-flow) conditions, KG1a cells displayed random motility and traction profiles that varied with time. In contrast, cells exposed to shear flow generated persistent, polarized tractions aligned with the axis of migration. Population analysis showed that maximum RMS traction forces were significantly elevated during upstream migration compared to static conditions (mean: 428.5 ± 63.0 nN vs 220.8 ± 22.2 nN, p = 0.0078), as were average RMS forces (mean: 82.6 ± 12.9 nN vs 45.9 ± 4.4 nN, p = 0.0184), while minimum force values remained comparable between groups. These findings indicate a specific amplification of stresses required to overcome applied forces during upstream migration. By integrating single-cell and population-level force analyses, this study defines upstream migration as a mechanically reinforced state characterized by amplified, directionally coherent traction dynamics. Our methods enable future dissection of the molecular regulators that coordinate force generation with migration under flow.

Efficacy and safety of pyruvate kinase activator in treating hemolytic anemias: a systematic review

2025-06-17

Syed Hassan Ahmed , Laila Tul Qadar , Jawad Ahmed +3 more | Expert Review of Hematology

Pyruvate kinase (PK) is an important glycolytic enzyme responsible for erythrocytic ATP production. PK allosteric activators have been shown to increase ATP and reduce 2,3-disphosphoglycerate among red blood cells leading … Pyruvate kinase (PK) is an important glycolytic enzyme responsible for erythrocytic ATP production. PK allosteric activators have been shown to increase ATP and reduce 2,3-disphosphoglycerate among red blood cells leading to improved oxygen affinity, sickling, and hemolysis. In this systematic review, we aim to evaluate the efficacy and safety of PK activators in hemolytic anemias. This study was conducted following the PRISMA guidelines. A literature search was conducted using relevant keywords over PubMed/Medline, Google Scholar, Cochrane Library, and clinicaltrial.gov, till 29 September 2024. Relevant data was extracted into a spreadsheet and synthesized qualitatively. The literature search yielded 7,153 results, with 7 studies ultimately included in the review. These studies involved 206 patients, 166 of whom received mitapivat and the rest received placebo. Hemoglobin response was achieved by 38.0% to 80.0% of participants receiving mitapivat, with an average increase of 0.4 to 1.7 g/dL. Most studies reported improvements in bilirubin, lactate dehydrogenase, haptoglobin, and reticulocyte levels. Adverse events (AEs) were experienced by 93.2% of participants, with rates of 93.97% and 89.7% in the intervention and control groups, respectively. However, most AEs were mild and transient, and 23.4% were graded as 3 or higher. In this study, PK activators, particularly mitapivat, demonstrated promising efficacy and safety profiles in managing hemolytic anemias. These agents significantly improved hemoglobin levels, markers of hemolysis, and hematopoietic response, offering a beneficial therapeutic option for various hemolytic conditions, including pyruvate kinase deficiency, sickle cell disease, and thalassemia. A protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) before study initiation, CRD42024598980.

Effects of vincristine on the properties of low threshold mechanoreceptors and high threshold mechanoreceptors in the hindpaw glabrous skin of mice

2025-06-17

Akihiro Yamada , Ayaka I. Yamada , Jennifer Ling +1 more | Molecular Brain

Abstract Vincristine is an important chemotherapy drug to treat various types of cancer, but it induces peripheral neuropathy, leading to numbness and mechanical allodynia in the hands and feet of … Abstract Vincristine is an important chemotherapy drug to treat various types of cancer, but it induces peripheral neuropathy, leading to numbness and mechanical allodynia in the hands and feet of patients. The peripheral neuropathy is a dose-limiting toxicity of vincristine chemotherapy. How vincristine treatment causes numbness and mechanical allodynia remains incompletely understood. In the present study, we utilized Nav1.8-ChR2 transgenic mice in which Nav1.8-ChR2-positive and Nav1.8-ChR2-negative mechanoreceptors could be characterized using the opto-electrophysiological method. Nav1.8-ChR2-negative Aβ- and Aδ-fiber mechanoreceptors are primarily low-threshold mechanoreceptors (LTMRs). On the other hand, Nav1.8-ChR2-positive Aβ- and Aδ-fiber mechanoreceptors are mainly high-threshold mechanoreceptors (HTMRs). We have shown that the mechanical threshold of Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors, but not Nav1.8-ChR2-negative Aδ-fiber mechanoreceptors, were increased significantly in the animals treated with vincristine. In contrast, the mechanical threshold of Nav1.8-ChR2-positive Aβ-fiber mechanoreceptors were significantly reduced following vincristine treatment. Vincristine treatment did not significantly affect the mechanical sensitivity of Nav1.8-ChR2-positive Aδ- and C-fiber mechanoreceptors. Vincristine treatment also did not affect the opto-sensitivity of Nav1.8-ChR2-positive Aβ-, Aδ-, and C-fiber mechanoreceptors. Our findings suggest that mechanical sensitivity is decreased in Aβ-fiber LTMRs and increased in Aβ-HTMRs following vincristine treatment, providing insights into vincristine-induced numbness and mechanical allodynia.

Local resonance of mechanosensitive channels

2025-06-17

Bing Qi , Shujuan Lin , Yaohua Guo +6 more | Journal of the Mechanics and Physics of Solids

Intracellular and nuclear CXCR4 signaling promotes terminal erythroblast differentiation and enucleation

2025-06-17

Julia Gutjahr , Elin Hub , Caroline A Anderson +7 more | Science Signaling

The chemokine CXCL12 signals through its receptor CXCR4 to induce the migration of all leukocyte types and multiple other cell types. Here, we report that CXCR4 is expressed in mouse … The chemokine CXCL12 signals through its receptor CXCR4 to induce the migration of all leukocyte types and multiple other cell types. Here, we report that CXCR4 is expressed in mouse erythroblasts, the bone marrow erythroid precursors, in which it stimulates erythrocyte generation instead of chemotaxis. CXCR4 signaling promoted homeostatic erythroblast maturation and increased the expression of genes mainly involved in metabolism and chromatin organization. Consequently, genetic depletion of CXCR4 in erythroblasts inhibited late erythropoiesis and diminished bone marrow erythroid outputs. Binding of CXCL12 to CXCR4 stimulated its rapid endocytosis and translocation together with Gα i or phosphorylated β-arrestin1 into distinct intracellular compartments, including the nuclear envelope and nucleus. CXCL12 signaling promoted erythroblast elongation and the condensation and excentric positioning of nuclei and stimulated rapid perinuclear Ca 2+ transients that immediately preceded erythroblast enucleation. These findings highlight previously uncharacterized physiological roles for CXCR4 and bone marrow–derived CXCL12 in erythropoiesis.

Neonatal hereditary spherocytosis: a case report

2025-06-17

Carolina Coramusi , Natalia Lucangeli , Sarah Vadalà +2 more | The Italian Journal of Pediatrics/Italian journal of pediatrics

Mechanotransduction as a therapeutic target for brain tumours

2025-06-16

Lauren Gomes , Carlos Pardo-Pastor , Jody Rosenblatt +1 more | EBioMedicine

Haploidentical Hematopoietic Stem Cell Transplantation for the Treatment of Congenital Dyserythropoietic Anemia Combined with Thalassemia: A Report of Two Cases

2025-06-16

Changyu Yang , Jianhua Huang , Kun Yang +7 more | Research Square (Research Square)

<title>Abstract</title> Congenital dyserythropoietic anemia (CDA) comprises a heterogeneous group of rare hereditary disorders characterized by ineffective erythropoiesis and often presents with clinical features that overlap with thalassemia. Hematopoietic stem cell … <title>Abstract</title> Congenital dyserythropoietic anemia (CDA) comprises a heterogeneous group of rare hereditary disorders characterized by ineffective erythropoiesis and often presents with clinical features that overlap with thalassemia. Hematopoietic stem cell transplantation (HSCT) remains the only definitive curative intervention for CDA; however, experience with haploidentical HSCT in this population is limited, and the procedure is associated with considerable challenges. We report two pediatric cases of CDA coexisting with thalassemia who underwent haploidentical related donor HSCT using a novel conditioning regimen comprising three alkylating agents. This was combined with graft-versus-host disease prophylaxis utilizing posttransplant cyclophosphamide and anti-thymocyte globulin. Both patients achieved sustained engraftment, transfusion independence, and remained free of severe transplant-related complications. These cases demonstrate the feasibility and therapeutic potential of haploidentical HSCT for patients with CDA, even in the context of concomitant thalassemia.

Glucose and methylglucose transport in human red blood cells and ghosts

2025-06-14

Jesper Brahm | AJP Cell Physiology

Radioactive labelled D-glucose (GL) or 3-O-methylglucose (MG) efflux from human resealed red ghosts (GHO) or red blood cells (RBC) were determined by means of rapid filtration techniques. All efflux curves … Radioactive labelled D-glucose (GL) or 3-O-methylglucose (MG) efflux from human resealed red ghosts (GHO) or red blood cells (RBC) were determined by means of rapid filtration techniques. All efflux curves show a monoexponential course. Under conditions of self exchange ( SE, equilibrium exchange) and net efflux ( NE, zero-trans efflux) in GHO at 0, 10, 25, and 38 °C simple Michaelis-Menten like kinetics in terms of K ½ and J max apply at 1-200 mM GL. SE conditions: K ½,SE is 19.9, 16.4, 11.2, 18.0 mM and J max,SE is 8.7, 42.7, 209, 555 pmole/(cm 2 × s); NE conditions: K ½,NE is 9.0, 6.7, 6.5, 11.5 mM and J max,NE is 2.8, 18.7, 172, 680 pmole/(cm 2 × s). GL SE shows a broad pH dependence with a maximum around pH 7-9. Under SE conditions at 0-38°C, an overall apparent activation energy, E A , is 76 kJ/mole. E A decreases nonlinearly with increasing temperature. A simple two-phase analysis reveals E A of ≈87 kJ/mole at 0-25°C and ≈49 kJ/mole at 25-38°C. Under NE conditions E A shows a linear dependence of 110 kJ/mole at 0-38°C. The data disagree with studies showing a nonlinear E A of GL and MG transport related to temperature dependent phase transitions of the lipids in the membrane. Effluxes of GL and MG in normal sized and swollen RBC with/without 4 mM ATP are all monoexponential, rejecting that ATP generates a biphasic hexose flux pattern. Hetero-exchange with a series of hexoses shows that galactose is best in trans-stimulation, and fructose best in trans-inhibition of GL efflux. The results disagree with current complicated kinetics models.

Piezo1 Agonist Yoda1 Induces Rapid Relaxation in Cultured Airway Smooth Muscle Cells and Bronchodilation in Mouse Models

2025-06-13

Mingzhi Luo , Xiangrong Zhang , Jia Guo +7 more | American Journal of Respiratory Cell and Molecular Biology

Bronchodilators that relax airway smooth muscle cells (ASMCs) are essential for treating constrictive airway diseases such as asthma. However, the existing bronchodilators are often unable to control symptoms of severe … Bronchodilators that relax airway smooth muscle cells (ASMCs) are essential for treating constrictive airway diseases such as asthma. However, the existing bronchodilators are often unable to control symptoms of severe asthmatic patients, leaving a pressing need to search for alternatives. Recent studies indicate that the transmembrane mechanosensitive channel, Piezo1 may provide a novel target for bronchodilation as it mediates ASMCs relaxation via calcium signaling and activation of large-conductance calcium-activated potassium channels (BKCa), and Piezo1 specific agonist Yoda1 has been shown to reduce cell stiffness and traction force in cultured ASMCs after 24 h incubation. Thus in this study, we further explored the potential of Yoda1 for inducing rapid ASMCs relaxation and bronchodilation. We treated either cultured ASMCs or allergen-induced mouse models of asthma with Yoda1 at various doses, and then assessed the resulting variations in cell stiffness, traction force, and molecular signaling of cultured ASMCs, as well as in airway resistance of the mouse models. We found that exposure to Yoda1 rapidly decreased cell stiffness, traction force in association with induced calcium signaling and BKCa activation in cultured ASMCs, and reduced airway resistance in methacholine-challenged mice in a dose-dependent manner. These results indicate that chemical activation of Piezo1 with specific agonist Yoda1 was indeed capable of inducing bronchodilation by relaxing ASMCs, and thus provide insights into development of Piezo1 agonist-based novel bronchodilators for treating constrictive airway disorders such as asthma.

Regulation of PIEZO1 channel force sensitivity by interblade handshaking

2025-06-13

Katie A. Smith , Eulashini Chuntharpursat‐Bon , Oleksandr V. Povstyan +7 more | Science Advances

PIEZOs form trimeric calcium-permeable nonselective cationic channels that serve mechanical sensing needs across eukaryotic biology. Forces act on the channels by causing their curved blades to flatten and decompact, leading … PIEZOs form trimeric calcium-permeable nonselective cationic channels that serve mechanical sensing needs across eukaryotic biology. Forces act on the channels by causing their curved blades to flatten and decompact, leading to an activated state, but it is unclear how this is regulated to enable the channels to adapt to different contexts. To identify potential mechanisms, we performed coarse-grained and all-atom molecular dynamics simulations on human PIEZO1. We observed an interblade handshake interaction mediated by basic amino acid residues in two flexible helices coordinated with regulated anionic lipid phosphatidylinositol 4,5-bisphosphate. The interaction determined the resting configuration of the channel, blade curvature, compactness, and ion pore structure. In experiments, disruption of the handshake by neutralization of helix amino acids or phosphatidylinositol 4,5-bisphosphate depletion increased the channel’s sensitivity to membrane tension. Structural and amino acid sequence analysis for multiple PIEZOs predicted helix amino acid arrangements for varied handshaking intensity. We suggest a dynamic interaction in PIEZO channels that regulates force sensitivity.

Activation of mechanosensitive ion channel Piezo1 linking metabolic reprogramming and pro-inflammatory responses in hepatocellular carcinoma

2025-06-13

Juanfen Mo , Y. Zhang , Chenxi Cao +6 more | Cell Communication and Signaling

Majjagni: A Classical Ayurvedic Appraisal of Marrow Metabolism and its Pathogenetic Role in Majja Pradoshaja Vikara

2025-06-06

G Gill , Chhaju Ram Yadav , Sarika Yadav | International Research Journal of Ayurveda & Yoga

Introduction: In Ayurvedic physiology, Majjagni (the tissue-specific metabolic fire associated with Majja Dhatu) plays a critical role in the biotransformation, nourishment, and maintenance of bone marrow and neural tissues. Despite … Introduction: In Ayurvedic physiology, Majjagni (the tissue-specific metabolic fire associated with Majja Dhatu) plays a critical role in the biotransformation, nourishment, and maintenance of bone marrow and neural tissues. Despite its critical significance, the precise physiological and pathological dimensions of Majjagni, particularly in the context of Majja Pradoshaja Vikara, remain under-defined within classical discourse.

Molecular rotors offer tool for evaluating red blood cell disorders

2025-06-06

Avery Thompson | Scilight

Fluorescent molecules that respond to changes in viscosity could provide a fast, accurate tool to probe the mechanical properties of individual cells. Fluorescent molecules that respond to changes in viscosity could provide a fast, accurate tool to probe the mechanical properties of individual cells.

Roles of Pyruvate Kinase M2 in Pulmonary Diseases: What Do We Know So Far?

2025-06-04

Diandian Li , Lian Liu , Jiangyue Qin +2 more | Lung

Preliminary research indicates that mechanical force through Pioze1 enhances local immunity during NPWT treatment for spinal infections

2025-06-03

Hao Xing , James C. Pan , Yue Chang +2 more | Frontiers in Immunology

This study aims to investigate the mechanism by which Negative Pressure Wound Therapy (NPWT) regulates local immune responses in spinal infection through Piezo1-mediated mechanical stress, and elucidate its potential role … This study aims to investigate the mechanism by which Negative Pressure Wound Therapy (NPWT) regulates local immune responses in spinal infection through Piezo1-mediated mechanical stress, and elucidate its potential role in the treatment of spinal infections. From July 2021 to April 2022, a total of 7 patients with spinal infection treated with NPWT at our department were included in the study. The study analyzed clinical outcomes of spinal infection surgeries, including operative duration, intraoperative blood loss, postoperative drainage, improvements in pain levels as measured by the Visual Analogue Scale (VAS), and inflammatory markers such as C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR) measured one week before and after the procedure. Additionally, healing times and recurrence rates within two years post-surgery were assessed. In addition, lesion specimens were retained during surgery and changes in Piezo1, Interleukin-1β (IL-1β), IL-6, IL-8, and Tumor Necrosis Factor-α (TNF-α) in lesion tissues were observed before and after immunohistochemical analysis. All 7 patients with spinal infections successfully underwent NPWT treatment and were ultimately cured. The average healing time was 45.71 ± 9.49 days, and there were no cases of recurrence or death during the two-year follow-up period. Surgical data showed a surgery duration of 96.57 ± 13.31 minutes, intraoperative blood loss of 65.71 ± 29.36 milliliters, and postoperative drainage of 163.57 ± 11.07 milliliters. Postoperatively, CRP, ESR, and VAS all significantly improved compared to preoperative levels (all p<0.05), which was superior to traditional treatment methods. Following NPWT intervention, the expression of Piezo1 protein at the lesion site significantly increased (0.03 ± 0.11 vs. 0.27 ± 0.22; p<0.05), while the expression levels of IL-1β, IL-6, IL-8, and TNF-α in the local immune microenvironment of the infected lesion significantly decreased (0.26 ± 0.11 vs. 0.16 ± 0.09, 0.27 ± 0.12 vs. 0.15 ± 0.67, 0.26 ± 0.18 vs. 0.10 ± 0.12, 0.35 ± 0.21 vs. 0.15 ± 0.11; p<0.05). Clinical results demonstrate that NPWT treatment for spinal infections exhibits remarkable efficacy, accompanied by a notable augmentation in local Piezo1 protein consistency. It is hypothesized that the mechanical force employed in NPWT treatment stimulates the Piezo1 protein, thereby modulating local immune cells and factors, ultimately bolstering local immunity. This study not only provides a molecular biology basis for a deeper understanding of the therapeutic effects of NPWT, but also offers new insights for optimizing treatment strategies for spinal infections.

Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons

2025-06-03

Pa Reum Lee , Kihwan Lee , Ji Min Park +2 more | International Journal of Oral Science

Piezo2, a mechanosensitive ion channel, serves as a crucial mechanotransducer in dental primary afferent (DPA) neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients. … Piezo2, a mechanosensitive ion channel, serves as a crucial mechanotransducer in dental primary afferent (DPA) neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients. Given Piezo2's widespread expression across diverse subpopulations of DPA neurons, this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels (VGSCs) and neuropeptide profiles. Using whole-cell patch-clamp recordings, we observed mechanically activated action potentials (APs) and classified AP waveforms based on the presence or absence of a hump during the repolarization phase. Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties, including tetrodotoxin-resistant VGSCs (NaV1.8 and NaV1.9) and TRPV1 expression. Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides-including two CGRP isoforms (α-CGRP and β-CGRP), Substance P, and Galanin-and the expression of NaV1.8 and NaV1.9, which were linked to defined AP subtypes. These molecular associations were further validated in Piezo2+ DPA neurons using fluorescence in situ hybridization. Together, these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.

Three novel heterozygous ANK1 loss-of-function variants cause hereditary spherocytosis in Chinese families

2025-06-03

Yang Wang , Tao Liu , Wen Wang +6 more | Annals of Hematology

Hereditary spherocytosis (HS) is an inherited hemolytic anemia caused by variants in red blood cell cytoskeleton proteins. Advances in sequencing technology have revealed numerous novel variants; however, accurate genome annotation … Hereditary spherocytosis (HS) is an inherited hemolytic anemia caused by variants in red blood cell cytoskeleton proteins. Advances in sequencing technology have revealed numerous novel variants; however, accurate genome annotation remains a significant challenge. In precision medicine, the precise identification of variants responsible for genetic diseases is crucial. This study aims to clearly delineate pathogenic variants and provide targeted pathogenicity analyses. We analyzed clinical data from three unrelated Chinese families with HS. Our investigation delved into the pathogenicity and underlying mechanisms of these variants. In silico simulations and in vitro experiments were employed to assess the effects of the identified variants. We identified three novel heterozygous variants in the ANK1 gene: c.558delG (p.R187Afs*66), c.728T > G (p.L243R), and c.3157 C > T (p.R1053X). In silico analysis indicated that these variants adversely affect the ankyrin-1. Functional studies demonstrated that these variants disrupt the synthesis of ankyrin-1, weakening its interaction with other red blood cell cytoskeleton proteins, which may lead to HS due to the loss of ankyrin-1 function. Our study offers valuable insights into the molecular mechanisms associated with HS linked to three de novo ANK1 variants. These findings deepen our understanding of the pathogenesis of HS and emphasize the critical role of genetic screening in the diagnosis of this condition.

Regeneration alters open chromatin andcis-regulatory landscape of erythroid precursors

2025-06-02

Yichao Zhou , Venkatasai Rahul Dogiparthi , Hannah L. Harris +7 more | Genome Research

Stress erythropoiesis elevates the rate of red blood cell (RBC) production as a physiological response to stressors such as anemia or hypoxia. In acute anemia, RBC progenitors and precursors temporarily … Stress erythropoiesis elevates the rate of red blood cell (RBC) production as a physiological response to stressors such as anemia or hypoxia. In acute anemia, RBC progenitors and precursors temporarily rewire their transcriptome, up- and downregulating hundreds of genes to accelerate the production of mature RBCs. Effective regeneration requires communication between critical cytokine signals (e.g., BMP4) and cis -regulatory elements on chromatin which coordinate transcriptional changes. To identify cis -regulatory changes that underlie anemia-specific gene expression and cellular responses, we analyzed chromatin accessibility in populations of cells enriched for red blood cell precursors isolated from mice at a range of time points after anemia induction. Early in the anemia response, chromatin is transiently open at AP-1-containing regions, correlated with increased Jun and Fos transcript/protein levels. Jun knockdown ex vivo decreases the percentage of KIT + erythroid precursors after anemia induction. We observe a second rewiring event at time points consistent with anemia resolution, involving repression of GATA factor-accessible regions and activation of ETS factor-accessible regions. In both mouse in vivo models and human CD34 + cells stimulated with BMP4, accessibility changes at regions with prior associations to human blood phenotypes. Dozens of BMP4- and anemia-activated loci are sensitive to natural human variation. The representation of red blood cell trait–associated loci in ATAC-seq data remains durably elevated more than 1 month after anemia resolution. Together, these findings provide a framework to understand the early establishment and late resolution of a regeneration-dependent transcriptome in RBC precursors.