megakaryocytes

Summary

Summary: Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.

Top Publications

  1. ncbi Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors
    Stephane Giraudier
    INSERM U362, Pavillon de Recherche 1, Institut Gustave Roussy, Villejuif Cedex, France Laboratoire d Hématologie and Laboratoire de Toxicologie, Hopital Henri Mondor, Creteil, France
    Blood 100:2932-40. 2002
  2. ncbi Megakaryocyte development and platelet production
    Varda R Deutsch
    The Haematology Institute, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel
    Br J Haematol 134:453-66. 2006
  3. pmc Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells
    Naoya Takayama
    Stem Cell Bank, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, Tokyo, Japan
    J Exp Med 207:2817-30. 2010
  4. pmc Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators
    Marloes R Tijssen
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK
    Dev Cell 20:597-609. 2011
  5. pmc Megakaryocytic differentiation induced by constitutive activation of mitogen-activated protein kinase kinase
    A M Whalen
    Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309, USA
    Mol Cell Biol 17:1947-58. 1997
  6. pmc Hematopoietic, angiogenic and eye defects in Meis1 mutant animals
    Tomoyuki Hisa
    Center for Cancer Research, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, USA
    EMBO J 23:450-9. 2004
  7. doi Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage
    Voahangy Randrianarison-Huetz
    Institut Cochin, Universite Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France
    Blood 115:2784-95. 2010
  8. doi p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation
    J L Sardina
    Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca, Spain
    Cell Death Differ 17:1842-54. 2010
  9. doi Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors
    Naoya Takayama
    Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Blood 111:5298-306. 2008
  10. doi The mitogen-activated protein kinase signaling pathways: role in megakaryocyte differentiation
    S Severin
    Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
    J Thromb Haemost 8:17-26. 2010

Research Grants

  1. Cellular and Molecular Regulation of Thrombopoiesis
    Ramesh A Shivdasani; Fiscal Year: 2012
  2. ANGARA KONETI RAO; Fiscal Year: 2016
  3. Melissa A Kacena; Fiscal Year: 2015
  4. Pro-inflammatory role of megakaryocytes in arthritis
    Peter A Nigrovic; Fiscal Year: 2013
  5. A Valance Washington; Fiscal Year: 2015
  6. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
  7. Caroline A Genco; Fiscal Year: 2014
  8. Louis M Pelus; Fiscal Year: 2016
  9. MICHAEL ALLAN HOLINSTAT; Fiscal Year: 2016
  10. Diane S Krause; Fiscal Year: 2016

Detail Information

Publications344 found, 100 shown here

  1. ncbi Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors
    Stephane Giraudier
    INSERM U362, Pavillon de Recherche 1, Institut Gustave Roussy, Villejuif Cedex, France Laboratoire d Hématologie and Laboratoire de Toxicologie, Hopital Henri Mondor, Creteil, France
    Blood 100:2932-40. 2002
    ..mechanisms involved in this spontaneous growth, we searched for genes differentially expressed between normal megakaryocytes requiring cytokines to grow and IMF spontaneously proliferating megakaryocytes...
  2. ncbi Megakaryocyte development and platelet production
    Varda R Deutsch
    The Haematology Institute, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel
    Br J Haematol 134:453-66. 2006
    ..Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease state, and the new approaches to thrombopoietic therapy...
  3. pmc Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells
    Naoya Takayama
    Stem Cell Bank, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, Tokyo, Japan
    J Exp Med 207:2817-30. 2010
    ..In contrast, sustained and excessive c-MYC expression in megakaryocytes was accompanied by increased p14 (ARF) and p16 (INK4A) expression, decreased GATA1 expression, and impaired ..
  4. pmc Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators
    Marloes R Tijssen
    Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK
    Dev Cell 20:597-609. 2011
    ..the five key hematopoietic transcription factors--GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL--in primary human megakaryocytes. Statistical analysis of the 17,263 regions bound by at least one factor demonstrated that simultaneous ..
  5. pmc Megakaryocytic differentiation induced by constitutive activation of mitogen-activated protein kinase kinase
    A M Whalen
    Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309, USA
    Mol Cell Biol 17:1947-58. 1997
    ....
  6. pmc Hematopoietic, angiogenic and eye defects in Meis1 mutant animals
    Tomoyuki Hisa
    Center for Cancer Research, Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, USA
    EMBO J 23:450-9. 2004
    ..They also fail to produce megakaryocytes, display extensive hemorrhaging, and die by embryonic day 14.5...
  7. doi Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage
    Voahangy Randrianarison-Huetz
    Institut Cochin, Universite Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Paris, France
    Blood 115:2784-95. 2010
    ..We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors...
  8. doi p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation
    J L Sardina
    Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca, Spain
    Cell Death Differ 17:1842-54. 2010
    ..We suggest that this might also be important for in vivo megakaryocytopoiesis...
  9. doi Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors
    Naoya Takayama
    Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Blood 111:5298-306. 2008
    ..and CD45, and were able to form hematopoietic colonies in semisolid culture and to differentiate into mature megakaryocytes by day 24 in the presence of thrombopoietin...
  10. doi The mitogen-activated protein kinase signaling pathways: role in megakaryocyte differentiation
    S Severin
    Centre for Cardiovascular Sciences, Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
    J Thromb Haemost 8:17-26. 2010
    Megakaryopoiesis is a process by which bone marrow progenitor cells develop into mature megakaryocytes (MKs), which in turn produce platelets required for normal hemostasis...
  11. doi Involvement of ERK1/2, p38 and PI3K in megakaryocytic differentiation of K562 cells
    Isabel Conde
    Department of Cellular and Molecular Medicine, Centro de Investigaciones Biologicas CSIC, Madrid, Spain
    Eur J Haematol 84:430-40. 2010
    ..In our experimental conditions, only STA-treated cells showed the phenotype of mature megakaryocytes (MKs) including GPIbalpha expression, DNA endoreduplication, and formation of platelet-like structures...
  12. pmc Protein-arginine methyltransferase 1 suppresses megakaryocytic differentiation via modulation of the p38 MAPK pathway in K562 cells
    Yuan I Chang
    Institute of Biopharmaceutical Sciences, National Yang Ming University, Taipei 11221, Taiwan
    J Biol Chem 285:20595-606. 2010
    ..We propose modulation of the p38 MAPK pathway by PRMT1 as a novel mechanism regulating megakaryocytic differentiation. This study thus provides a new perspective on the promotion of megakaryopoiesis...
  13. pmc Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets
    R Mohle
    Developmental Hematopoiesis Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 94:663-8. 1997
    ..endothelial cells with hematopoietic progenitor cells results in proliferation and differentiation of megakaryocytes. In these long-term cultures, bone marrow microvascular endothelial cell monolayers maintain their cellular ..
  14. ncbi RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation
    Kamaleldin E Elagib
    Department of Pathology, University of Virginia, Charlottesville, VA 22908 0904, USA
    Blood 101:4333-41. 2003
    ..bone marrow confirmed a strong expression of RUNX1 and its cofactor, core-binding factor beta (CBFbeta), in megakaryocytes and a minimal expression in erythroblasts...
  15. pmc Historical review: megakaryopoiesis and thrombopoiesis
    Kenneth Kaushansky
    Department of Medicine, University of California, San Diego, CA 92103 8811, USA
    Blood 111:981-6. 2008
    ..During this time megakaryocytes were identified as the origin of blood platelets; marrow-derived megakaryocytic progenitor cells were ..
  16. ncbi Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis
    Scott T Avecilla
    Department of Medicine, Division of Hematology Oncology, Cornell University Medical College, 1300 York Avenue, New York, New York 10021, USA
    Nat Med 10:64-71. 2004
    ..Progenitor-active chemokines offer a new strategy to restore hematopoiesis in a clinical setting...
  17. ncbi A role for the MEK/MAPK pathway in PMA-induced cell cycle arrest: modulation of megakaryocytic differentiation of K562 cells
    R Herrera
    Department of Cell Biology, Parke Davis Pharmaceutical Research Division of Warner Lambert Company, Ann Arbor, Michigan 48105, USA
    Exp Cell Res 238:407-14. 1998
    ....
  18. doi Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow
    Oliver Winter
    Institute for Systemic Inflammation Research, University of Lubeck, Ratzeburger Allee 160, Lubeck, Germany
    Blood 116:1867-75. 2010
    ..Here, we demonstrate that, within the bone marrow, plasma cells interact with the platelet precursors (megakaryocytes), which produce the prominent plasma cell survival factors APRIL (a proliferation-inducing ligand) and IL-6 (..
  19. doi Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis
    Irina Pleines
    Chair of Vascular Medicine, University Hospital Würzburg and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Josef Schneider Strasse 2, Wurzburg, Germany
    Blood 119:1054-63. 2012
    ..Together, these results establish RhoA as an important regulator of platelet function in thrombosis and hemostasis...
  20. pmc Induction of functional platelets from mouse and human fibroblasts by p45NF-E2/Maf
    Yukako Ono
    Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
    Blood 120:3812-21. 2012
    Determinant factors leading from stem cells to megakaryocytes (MKs) and subsequently platelets have yet to be identified...
  21. ncbi Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis
    M Majka
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Blood 96:4142-51. 2000
    ..This study expands the understanding of the role of SDF-1 and TPO in normal human megakaryopoiesis and indicates the molecular basis of the observed differences in cellular responses. (Blood. 2000;96:4142-4151)..
  22. ncbi Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development
    R A Shivdasani
    Division of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cell 81:695-704. 1995
    ..the importance of blood platelets in health and disease, the mechanisms regulating their formation within megakaryocytes are unknown...
  23. ncbi Deficiency in the Wiskott-Aldrich protein induces premature proplatelet formation and platelet production in the bone marrow compartment
    Siham Sabri
    Institut National de la Santé etde la Recherche Médicale INSERM, U790, Universite Paris XI, Institut Gustave Roussy, Villejut, France
    Blood 108:134-40. 2006
    ..WASp-deficient megakaryocytes (MKs) also displayed defects in response to fibrillar collagen I (CI) in vitro, the major matrix component of ..
  24. doi A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis
    Olena Klimchenko
    INSERM U790, Institut Gustave Roussy, Villejuif, France
    Blood 114:1506-17. 2009
    ..This novel MEP differentiation system may allow an in-depth exploration of the molecular bases of erythroid and MK commitment and differentiation...
  25. pmc Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice
    Shi Jiang Lu
    Stem Cell and Regenerative Medicine International, 33 Locke Drive, Marlborough, MA 01752, USA
    Cell Res 21:530-45. 2011
    ..In this study, we report that it is feasible to generate functional megakaryocytes and platelets from human embryonic stem cells (hESCs) on a large scale...
  26. pmc Infusion of mature megakaryocytes into mice yields functional platelets
    Rudy Fuentes
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Clin Invest 120:3917-22. 2010
    Thrombopoiesis, the process by which circulating platelets arise from megakaryocytes, remains incompletely understood. Prior studies suggest that megakaryocytes shed platelets in the pulmonary vasculature...
  27. pmc A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
    Lin Zhang
    Medizinische Klinik und Poliklinik I, Klinikum der Universitat, Ludwig Maximilian Universitat Munchen, 81337 Munich, Germany
    J Exp Med 209:2165-81. 2012
    Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood...
  28. ncbi Development of hematopoietic cells lacking transcription factor GATA-1
    L Pevny
    Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032
    Development 121:163-72. 1995
    ..factor believed to play an important role in gene regulation during the development of erythroid cells, megakaryocytes and mast cells...
  29. ncbi Alpha-granule membrane mirrors the platelet plasma membrane and contains the glycoproteins Ib, IX, and V
    G Berger
    INSERM U91, Hopital Henri Mondor, Creteil, France
    Blood 87:1385-95. 1996
    ..subjects, patients with Bernard-Soulier syndrome, patients with Gray platelet syndrome, and human cultured megakaryocytes. Ultra-thin sections of the cells were labeled with antibodies directed against glycocalicin, GPIb, GPIX, and ..
  30. ncbi Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia
    W J Song
    Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Nat Genet 23:166-75. 1999
    ..Our findings support a model for FPD/AML in which haploinsufficiency of CBFA2 causes an autosomal dominant congenital platelet defect and predisposes to the acquisition of additional mutations that cause leukaemia...
  31. ncbi EVI1 is expressed in megakaryocyte cell lineage and enforced expression of EVI1 in UT-7/GM cells induces megakaryocyte differentiation
    Seiichi Shimizu
    Department of Biochemistry, Miyazaki Medical College, Miyazaki, Japan
    Biochem Biophys Res Commun 292:609-16. 2002
    ..various types of hematopoietic cells revealed that the EVI1 gene is expressed specifically in CD34(+) cells, megakaryocytes, and platelets...
  32. pmc The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12
    Mark A Hall
    Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia
    Proc Natl Acad Sci U S A 100:992-7. 2003
    ..These results suggest that SCL is critical for megakaryopoiesis and erythropoiesis, but is dispensable for production of myeloid cells during adult hematopoiesis...
  33. ncbi c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation
    Mark L Sandberg
    Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA
    Dev Cell 8:153-66. 2005
    ..Cell cycle analyses show that twice as many HSCs from c-Myb(M303V/M303V) animals are actively cycling. Thus c-Myb, through interaction with p300, controls the proliferation and differentiation of hematopoietic stem and progenitor cells...
  34. ncbi Increased megakaryocytopoiesis in Lyn-deficient mice
    B J Lannutti
    Puget Sound Blood Center, Seattle, WA, USA
    Oncogene 25:3316-24. 2006
    ..In addition, colony-forming unit-megakaryocytes (CFU-MK) are increased and TPO-induced expansion of primary marrow cells yielded a greater number of mature ..
  35. pmc Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis
    Harald Schulze
    Dana Farber Cancer Institute, One Jimmy Fund Way, Boston, MA 02115, USA
    Blood 107:3868-75. 2006
    To produce blood platelets, megakaryocytes elaborate proplatelets, accompanied by expansion of membrane surface area and dramatic cytoskeletal rearrangements...
  36. pmc Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization
    Andrew G Muntean
    Graduate Program in Molecular Genetics and Cell Biology, University of Chicago, IL, USA
    Blood 109:5199-207. 2007
    Endomitosis is a unique form of cell cycle used by megakaryocytes, in which the latter stages of mitosis are bypassed so that the cell can increase its DNA content and size...
  37. pmc 15-deoxy-delta12,14-PGJ2 enhances platelet production from megakaryocytes
    Jamie J O'Brien
    Department of Environmental Medicine and the Lung Biology and Disease Program, University of Rochester, NY, USA
    Blood 112:4051-60. 2008
    ..15d-PGJ(2) also promotes platelet formation from culture-derived mouse and human megakaryocytes and accelerates platelet recovery after in vivo radiation-induced bone marrow injury...
  38. doi Mutation of the beta1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly
    Shinji Kunishima
    Department of Hemostasis and Thrombosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
    Blood 113:458-61. 2009
    ..Large and irregular bleb protrusions observed in megakaryocytes derived from the patient's peripheral blood CD34(+) cells suggested impaired megakaryocyte fragmentation and ..
  39. pmc Bone marrow osteoblastic niche: a new model to study physiological regulation of megakaryopoiesis
    Isabella Pallotta
    Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, USA
    PLoS ONE 4:e8359. 2009
    The mechanism by which megakaryocytes (Mks) proliferate, differentiate, and release platelets into circulation are not well understood...
  40. pmc Platelet formation
    Jonathan N Thon
    Translational Medicine Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    Semin Hematol 47:220-6. 2010
    ..the thrombopoietin receptor are currently available, the development of drugs that directly stimulate megakaryocytes to generate platelets has lagged behind...
  41. pmc Biology and chemistry of thrombopoietic agents
    David J Kuter
    Hematology Division, Massachusetts General Hospital, Boston, MA 02114, USA
    Semin Hematol 47:243-8. 2010
    ..eTPO) regulates platelet production by increasing the number, ploidy, and maturation rate of bone marrow megakaryocytes. Early attempts to treat thrombocytopenia by the administration of recombinant TPO were successful but were ..
  42. pmc Developmental differences in megakaryocytopoiesis are associated with up-regulated TPO signaling through mTOR and elevated GATA-1 levels in neonatal megakaryocytes
    Zhi jian Liu
    Division of Newborn Medicine, Children s Hospital Boston, Boston, MA, USA
    Blood 117:4106-17. 2011
    ....
  43. doi Heterozygous ITGA2B R995W mutation inducing constitutive activation of the αIIbβ3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia
    Shinji Kunishima
    Department of Advanced Diagnosis, Clinical Research Center, National Hospital Organization Nagoya Medical Center, 4 1 1 Sannomaru, Naka ku, Nagoya, Japan
    Blood 117:5479-84. 2011
    ..increased size and decreased number of proplatelet tips in αIIb-W995/β3-transduced mouse fetal liver-derived megakaryocytes indicate defective pro-platelet formation...
  44. pmc Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification
    Melanie G Cornejo
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 118:1264-73. 2011
    ....
  45. pmc Myosin-II inhibition and soft 2D matrix maximize multinucleation and cellular projections typical of platelet-producing megakaryocytes
    Jae Won Shin
    Pharmacology Graduate Group, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 108:11458-63. 2011
    ..a rigid matrix are all promoted by myosin-II, and so multinucleated cells with distended membranes--typical of megakaryocytes (MKs)--seem predictable for low myosin activity in cells on soft matrices...
  46. doi Caspase-9 mediates the apoptotic death of megakaryocytes and platelets, but is dispensable for their generation and function
    Michael J White
    Cancer and Hematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Blood 119:4283-90. 2012
    Apoptotic caspases, including caspase-9, are thought to facilitate platelet shedding by megakaryocytes. They are known to be activated during platelet apoptosis, and have also been implicated in platelet hemostatic responses...
  47. doi RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization
    Larissa Lordier
    INSERM UMR 1009, Institut Gustave Roussy, 114, rue Edouard Vaillant, Villejuif 94805, France
    Nat Commun 3:717. 2012
    b>Megakaryocytes are unique mammalian cells that undergo polyploidization (endomitosis) during differentiation, leading to an increase in cell size and protein production that precedes platelet production...
  48. pmc A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site
    Sylvia T Nürnberg
    Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge, United Kingdom
    Blood 120:4859-68. 2012
    ..Platelets are formed in the bone marrow by megakaryocytes, which are derived from hematopoietic stem cells by a process mainly controlled by transcription factors...
  49. ncbi Thrombopoietin induces phosphoinositol 3-kinase activation through SHP2, Gab, and insulin receptor substrate proteins in BAF3 cells and primary murine megakaryocytes
    Y Miyakawa
    Division of Hematology, University of Washington School of Medicine, Seattle 98195, USA
    J Biol Chem 276:2494-502. 2001
    ....
  50. ncbi Thrombopoietin, but not cytokines binding to gp130 protein-coupled receptors, activates MAPKp42/44, AKT, and STAT proteins in normal human CD34+ cells, megakaryocytes, and platelets
    Marcin Majka
    Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA
    Exp Hematol 30:751-60. 2002
    The development of megakaryocytes is regulated by thrombopoietin (TPO), which binds to the c-mpl receptor, and by several other cytokines such as interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), cilliary neurotropic factor (..
  51. pmc ETO-2 associates with SCL in erythroid cells and megakaryocytes and provides repressor functions in erythropoiesis
    Anna H Schuh
    MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
    Mol Cell Biol 25:10235-50. 2005
    ..Importantly, SCL/ETO-2 interacts with another corepressor, Gfi-1b, in red cells but not megakaryocytes. The SCL/ETO-2/Gfi-1b association is lost during erythroid differentiation of primary fetal liver cells...
  52. pmc Novel role for EKLF in megakaryocyte lineage commitment
    Pilar Frontelo
    Mount Sinai School of Medicine, New York, NY 10029, USA
    Blood 110:3871-80. 2007
    b>Megakaryocytes and erythroid cells are thought to derive from a common progenitor during hematopoietic differentiation...
  53. pmc Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis
    Christos Gekas
    Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA
    Blood 113:3461-71. 2009
    ..In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages...
  54. pmc Megakaryopoiesis
    Amy E Geddis
    Pediatric Hematology Oncology, University of California, San Diego, La Jolla, CA 92023, USA
    Semin Hematol 47:212-9. 2010
    ..b>Megakaryocytes are derived from the hematopoietic stem cell through successive lineage commitment steps, and they undergo a ..
  55. doi MYC accelerates p21CIP-induced megakaryocytic differentiation involving early mitosis arrest in leukemia cells
    Maria J Munoz-Alonso
    Departamento de Biologia Molecular, Universidad de Cantabria, Santander, Spain
    J Cell Physiol 227:2069-78. 2012
    ..Our data suggests that in some systems p21(CIP) takes part in a mitosis control driving MYC-induced cellular growth into differentiation...
  56. ncbi Megakaryocytopoiesis and thrombopoiesis in hematopoietic stem cells exposed to ionizing radiation
    Satoru Monzen
    Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66 1 Hon cho, Hirosaki, Aomori 036 8564, Japan
    Radiat Res 176:716-24. 2011
    ..This study examined the terminal maturation of megakaryocytes and platelet production in hematopoietic stem/progenitor cells (HSPCs) exposed to ionizing radiation...
  57. pmc Role of RhoA-specific guanine exchange factors in regulation of endomitosis in megakaryocytes
    Yuan Gao
    Department of Laboratory Medicine, Yale University, New Haven, CT 06520, USA
    Dev Cell 22:573-84. 2012
    Polyploidization can precede the development of aneuploidy in cancer. Polyploidization in megakaryocytes (Mks), in contrast, is a highly controlled developmental process critical for efficient platelet production via unknown mechanisms...
  58. pmc Regulatory effects of TLR2 on megakaryocytic cell function
    Lea M Beaulieu
    Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA
    Blood 117:5963-74. 2011
    TLR2, a functional, inflammatory-related receptor, is known to be expressed on megakaryocytes and platelets and to lead to infection and immune-mediated activation of platelets; however, the role of this receptor in megakaryocytes is not ..
  59. ncbi Roads to polyploidy: the megakaryocyte example
    Katya Ravid
    Department of Biochemistry, Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA
    J Cell Physiol 190:7-20. 2002
    ..number, has been described in plants, insects, and in mammalian cells such as, the platelet precursors, the megakaryocytes. Several of these cell types reach high ploidy via a different cell cycle...
  60. pmc In vitro megakaryocyte production and platelet biogenesis: state of the art
    Jo Anna Reems
    Puget Sound Blood Center, Seattle, WA 98104, USA
    Transfus Med Rev 24:33-43. 2010
    ....
  61. pmc Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets
    Emma C Josefsson
    Molecular Medicine Division, Cancer and Hematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Australia Department of Medical Biology, The University of Melbourne, Parkville 3010, Australia
    J Exp Med 208:2017-31. 2011
    It is believed that megakaryocytes undergo a specialized form of apoptosis to shed platelets...
  62. pmc Characterization of megakaryocyte GATA1-interacting proteins: the corepressor ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation
    Isla Hamlett
    Medical Research Council MRC Molecular Haematology Unit and Department of Haematology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
    Blood 112:2738-49. 2008
    ..approaches show that GATA1 interacts with several proteins in the megakaryocyte cell line L8057 and in primary megakaryocytes. They include FOG1, the NURD complex, the pentameric complex containing SCL/TAL-1, the zinc-finger regulators ..
  63. pmc Notch signaling specifies megakaryocyte development from hematopoietic stem cells
    Thomas Mercher
    Department of Medicine, Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 20115, USA
    Cell Stem Cell 3:314-26. 2008
    ..However, we unexpectedly observed the development of megakaryocytes when using heterotypic cocultures of hematopoietic stem cells with OP9 cells expressing Delta-like1, but not ..
  64. pmc NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development
    Annarita Miccio
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA, USA
    EMBO J 29:442-56. 2010
    ..Gene expression analysis in primary mutant erythroid cells and megakaryocytes (MKs) revealed an essential function for NuRD during both the repression and activation of select GATA-1/FOG-1 ..
  65. ncbi Differential regulation of actin stress fiber assembly and proplatelet formation by alpha2beta1 integrin and GPVI in human megakaryocytes
    Siham Sabri
    Institut National de la Sante et de la Recherche Medicale, U362, Institut Gustave Roussy, rue Camille Desmoulins, 94800 Villejuif, France
    Blood 104:3117-25. 2004
    ..The actin cytoskeleton plays a major role in platelet function. In contrast, its precise role in the function of megakaryocytes (MKs) is less understood but may be important for a chemoattractive response and an efficient proplatelet ..
  66. pmc Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes
    Sunita R Patel
    Division of Hematology, Brigham and Women s Hospital, Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Blood 106:4076-85. 2005
    b>Megakaryocytes are terminally differentiated cells that, in their final hours, convert their cytoplasm into long, branched proplatelets, which remodel into blood platelets. Proplatelets elongate at an average rate of 0...
  67. ncbi Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo
    Ralph Tiedt
    Department of Research and Experimental Hematology, University Hospital Basel, Switzerland
    Blood 109:1503-6. 2007
    ..Crossing Q3 mice with the ROSA26-lacZ reporter strain showed that Cre-recombinase activity was confined to megakaryocytes. These results were further verified by crossing the Q3 mice with a strain containing loxP-flanked integrin ..
  68. ncbi Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F
    K Shide
    Department of Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, Kiyotake, Miyazaki, Japan
    Leukemia 22:87-95. 2008
    ..They showed anemia that means Hb value from 9 to 10 g per 100 ml when 1 month old. Myeloid cells and megakaryocytes were predominant in the bone marrow of these animals, and splenomegaly was observed...
  69. pmc c-Myc-mediated control of cell fate in megakaryocyte-erythrocyte progenitors
    Yinshi Guo
    Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA
    Blood 114:2097-106. 2009
    ..corresponding progenitors, we found significantly increased numbers of megakaryocytic progenitors and mature megakaryocytes in bone marrow and spleens of c-Myc-knockout (c-Myc(-/-)) mice...
  70. pmc GATA-2 reinforces megakaryocyte development in the absence of GATA-1
    Zan Huang
    Division of Hematology and Oncology, Northwestern University, Lurie Research Building 5 113, Chicago, IL 60611, USA
    Mol Cell Biol 29:5168-80. 2009
    ..Furthermore, we demonstrate that GATA-2 indirectly controls cell cycle progression in GATA-1-deficient megakaryocytes. Genome-wide microarray analysis and chromatin immunoprecipitation studies revealed that GATA-2 regulates a ..
  71. ncbi AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis
    Motoshi Ichikawa
    Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo, 113 8655, Japan
    Nat Med 10:299-304. 2004
    ..AML-1 is thus required for maturation of megakaryocytes and differentiation of T and B cells, but not for maintenance of hematopoietic stem cells (HSCs) in adult ..
  72. pmc The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway
    Zhao Chen
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
    Blood 110:171-9. 2007
    ..The unexpected mechanism for Myh9-associated thrombocytopenia may lead to new molecular approaches to manipulate thrombopoiesis...
  73. ncbi Delivering new insight into the biology of megakaryopoiesis and thrombopoiesis
    Elisabeth M Battinelli
    Translational Medicine Division, Department of Medicine, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Curr Opin Hematol 14:419-26. 2007
    ..The aim of this review is to explore the state of the art knowledge on the cell biological and molecular pathways that regulate megakaryopoiesis and lead to platelet production...
  74. pmc Deletion of Mtg16, a target of t(16;21), alters hematopoietic progenitor cell proliferation and lineage allocation
    Brenda J Chyla
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mol Cell Biol 28:6234-47. 2008
    ..This impairment appears to be a failure to proliferate rather than an induction of cell death, as expression of c-Myc, but not Bcl2, complemented the Mtg16(-/-) defect...
  75. ncbi Molecular and transcriptional regulation of megakaryocyte differentiation
    R A Shivdasani
    Departments of Adult Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Stem Cells 19:397-407. 2001
    b>Megakaryocytes, among the rarest of hematopoietic cells, serve the essential function of producing numerous platelets...
  76. doi ADF/n-cofilin-dependent actin turnover determines platelet formation and sizing
    Markus Bender
    Rudolf Virchow Center, Deutsche Forschungsgemeinschaft Research Center for Experimental Biomedicine, University of Wurzburg, Wurzburg, Germany
    Blood 116:1767-75. 2010
    The cellular and molecular mechanisms orchestrating the complex process by which bone marrow megakaryocytes form and release platelets remain poorly understood...
  77. pmc MicroRNA expression in maturing murine megakaryocytes
    Joanna B Opalinska
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Blood 116:e128-38. 2010
    ..We examined global microRNA expression during the differentiation of murine hematopoietic progenitors into megakaryocytes. Of 435 miRNAs analyzed, 13 were up-regulated and 81 were down-regulated...
  78. doi Inducible Fli-1 gene deletion in adult mice modifies several myeloid lineage commitment decisions and accelerates proliferation arrest and terminal erythrocytic differentiation
    Joëlle Starck
    Universite de Lyon, Lyon, France
    Blood 116:4795-805. 2010
    ..Fli-1 deletion in adult induced mild thrombocytopenia associated with a drastic decrease in large mature megakaryocytes number...
  79. doi Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models
    Niv Pencovich
    Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
    Blood 117:e1-14. 2011
    ..megakaryocytic cell lines to characterize the network of RUNX1 targets and cooperating TFs in differentiating megakaryocytes and demonstrated how dynamic partnerships between RUNX1 and cooperating TFs facilitated regulatory plasticity ..
  80. pmc Transgenic, inducible RNAi in megakaryocytes and platelets in mice
    M Takiguchi
    Molecular Medicine Division Chemical Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia
    J Thromb Haemost 8:2751-6. 2010
    ....
  81. ncbi Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain
    S Avraham
    Deaconess Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 270:27742-51. 1995
    ..Expression of RAFTK was also observed in human CD34+ marrow cells, primary bone marrow megakaryocytes, platelets, and various areas of brain...
  82. ncbi Identification and characterization of a novel tyrosine kinase from megakaryocytes
    B D Bennett
    Division of Hematology Oncology, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215
    J Biol Chem 269:1068-74. 1994
    ..Based on its restriction in expression and its modulation during in vitro differentiation, it is likely that matk participates in signal transduction during megakaryocytopoiesis...
  83. pmc Properties of ets-1 binding to chromatin and its effect on platelet factor 4 gene expression
    Jun Lu
    Department of Biochemistry, Cancer Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Mol Cell Biol 24:428-41. 2004
    Ets-1 is important for transcriptional regulation in several hematopoietic lineages, including megakaryocytes. Some transcription factors bind to naked DNA and chromatin with different affinities, while others do not...
  84. pmc NF-E2 domination over Nrf2 promotes ROS accumulation and megakaryocytic maturation
    Hozumi Motohashi
    Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, 2 1 Seiryo cho, Aoba ku, Sendai 980 8575, Japan
    Blood 115:677-86. 2010
    In megakaryocytes, the maturation process and oxidative stress response appear to be closely related...
  85. pmc Mitochondrial localization of vitamin D receptor in human platelets and differentiated megakaryocytes
    Francesca Silvagno
    Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy
    PLoS ONE 5:e8670. 2010
    ..reported and VDR signalling has been characterized in monocytes and vascular cells, nothing is known about VDR expression and functions in human platelets, anucleated fragments of megakaryocytes which are known targets of other steroids.
  86. pmc Serum response factor is an essential transcription factor in megakaryocytic maturation
    Stephanie Halene
    Department of Internal Medicine and Yale Cancer Center, Section of Hematology, 333 Cedar Street, New Haven, CT 06520, USA
    Blood 116:1942-50. 2010
    ..In contrast, the BM has increased number and percentage of CD41(+) megakaryocytes (WT: 0.41% ± 0.06%; KO: 1.92% ± 0.12%) with significantly reduced ploidy...
  87. doi Congenital amegakaryocytic thrombocytopenia
    Amy E Geddis
    Pediatric Hematology Oncology, University of California San Diego, Rady Children s Hospital San Diego, San Diego, California 92123, USA
    Pediatr Blood Cancer 57:199-203. 2011
    ..presenting at birth in a child without congenital or skeletal malformations, reduced or absent bone marrow megakaryocytes, and eventual progression to bone marrow failure...
  88. doi Notch/Delta4 signaling inhibits human megakaryocytic terminal differentiation
    Sonia Poirault-Chassac
    Inserm U1009, Villejuif, France
    Blood 116:5670-8. 2010
    ..conditions, Dll4Fc strongly impaired platelet production by reducing the generation of mature CD41a(+)CD42b(+) megakaryocytes (MKs) and platelet-forming cells...
  89. doi Megakaryocyte-matrix interaction within bone marrow: new roles for fibronectin and factor XIII-A
    Alessandro Malara
    Department of Biochemistry, Istituto di Ricovero e Cura a Carattere Scientifico IRCCS San Matteo Foundation, University of Pavia, Pavia, Italy
    Blood 117:2476-83. 2011
    The mechanisms by which megakaryocytes (MKs) differentiate and release platelets into the circulation are not well understood...
  90. pmc ProxTom lymphatic vessel reporter mice reveal Prox1 expression in the adrenal medulla, megakaryocytes, and platelets
    Lucy A Truman
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06511, USA
    Am J Pathol 180:1715-25. 2012
    ..mice revealed the expression of Prox1 in three novel sites: the neuroendocrine cells of the adrenal medulla, megakaryocytes, and platelets. The novel sites identified herein suggest previously unknown roles for Prox1...
  91. ncbi Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines
    G Barosi
    Laboratory of Medical Informatics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S Matteo, Pavia, Italy
    J Clin Oncol 17:2954-70. 1999
    ....
  92. ncbi Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release
    Gianfranco Mattia
    Department of Clinical Biochemistry, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161, Rome, Italy
    Blood 99:888-97. 2002
    ..The data indicate the inability of the CB-MKs to progress in the endomitotic process and a direct correlation between DNA content and platelet production...
  93. ncbi Megakaryocyte-osteoblast interaction revealed in mice deficient in transcription factors GATA-1 and NF-E2
    Melissa A Kacena
    Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut 06520 8071, USA
    J Bone Miner Res 19:652-60. 2004
    ..Osteoblast proliferation increased up to 6-fold when cultured with megakaryocytes. A megakaryocyte-osteoblast interaction plays a role in the increased bone formation in these mice.
  94. ncbi Inhibition by Rho-kinase and protein kinase C of myosin phosphatase is involved in thrombin-induced shape change of megakaryocytic leukemia cell line UT-7/TPO
    Akira Yazaki
    The 2nd Department of Internal Medicine, Mie University School of Medicine, Mie 514 8507, Japan
    Cell Signal 17:321-30. 2005
    ....
  95. pmc An amphipathic motif at the transmembrane-cytoplasmic junction prevents autonomous activation of the thrombopoietin receptor
    Judith Staerk
    Ludwig Institute for Cancer Research, Universite Catholique de Louvain, Avenue Hippocrate 74, UCL 75 4, 1200 Brussels, Belgium
    Blood 107:1864-71. 2006
    ..These residues may be targets for activating mutations in humans. Such a motif may exist in other receptors to prevent ligand-independent activation and to allow signaling via multiple flexible interfaces...
  96. ncbi Megakaryocytes derived from human embryonic stem cells: a genetically tractable system to study megakaryocytopoiesis and integrin function
    M Gaur
    Department of Laboratory Medicine, University of California, San Francisco, CA 94142, USA
    J Thromb Haemost 4:436-42. 2006
    ..Furthermore, fibrinogen binding to alpha(IIb)beta(3) triggers cytoskeletal changes and granule release (outside-in signaling)...
  97. ncbi Thrombopoietin and its receptor
    F Wendling
    INSERM U 362, Institut Gustave Roussy, Villejuif, France
    Eur Cytokine Netw 9:221-31. 1998
    ..Preclinical and clinical studies demonstrate the potential use of TPO in a variety of contexts, but it is too early to evaluate its benefit in reducing platelet transfusion...
  98. ncbi Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes
    D J Price
    Divisions of Experimental Medicine and Hematology Oncology, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 272:5915-20. 1997
    ..This indicates that CHK binds to the same site on c-KIT to which FYN binds, possibly bringing the two into proximity on associated c-KIT subunits and leading to the down-regulation of FYN by CHK...
  99. pmc Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice
    J A Shavit
    Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208 3500 USA
    Genes Dev 12:2164-74. 1998
    ..These results provide direct evidence that the small Maf transcription factors are vital participants in embryonic development and cellular differentiation...
  100. ncbi The roles of phosphatidylinositol 3-kinase and protein kinase Czeta for thrombopoietin-induced mitogen-activated protein kinase activation in primary murine megakaryocytes
    P Rojnuckarin
    Division of Hematology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 276:41014-22. 2001
    ..that the ERK/mitogen-activated protein kinase pathway is important for TPO-induced endomitosis in primary megakaryocytes (MKs)...
  101. ncbi The birth of the platelet
    J Hartwig
    Hematology Division, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Thromb Haemost 1:1580-6. 2003
    Platelets are small subcellular fragments that are formed from the cytoplasm of bone marrow megakaryocytes, which circulate in blood with characteristic discoid shapes...

Research Grants73

  1. Cellular and Molecular Regulation of Thrombopoiesis
    Ramesh A Shivdasani; Fiscal Year: 2012
    ..Cellular and molecular mechanisms of platelet assembly within, and their release from, megakaryocytes (MKs) remain largely unknown...
  2. ANGARA KONETI RAO; Fiscal Year: 2016
    ..in transcription factor RUNX1 (Core binding factor A2, RUNX1) and into the genes regulated in platelets/ megakaryocytes by RUNX1 through studies in patients characterized with RUNX1 haplodeficiency...
  3. Melissa A Kacena; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): A growing body of evidence suggests that megakaryocytes (MKs) play a key role in regulating skeletal homeostasis...
  4. Pro-inflammatory role of megakaryocytes in arthritis
    Peter A Nigrovic; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Pro-inflammatory role of megakaryocytes in arthritis Project Summary In inflammatory arthritis, the joints become the focus of intense immunological attack, frequently leading to irreversible injury ..
  5. A Valance Washington; Fiscal Year: 2015
    ..TLT-1 is abundant, specific to platelets and megakaryocytes, and like p-selectin, stored in the platelet 1-granules...
  6. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
    ..procofactor, factor V, originates from plasma through endocytosis of factor V by platelet precursors, megakaryocytes, via a two receptor system consisting of a specific, as of yet, unidentified factor V receptor and LDL ..
  7. Caroline A Genco; Fiscal Year: 2014
    ..modulation of TLR2- and IL1R-dependent signaling pathways in platelets and NFkappaB-dependent transcription in megakaryocytes. Aim 3. To define the role of TLR2 and IL-1 R in platelet specific responses to C. pneumoniae and P...
  8. Louis M Pelus; Fiscal Year: 2016
    ..They have forged a new collaboration based upon the findings in the Kacena laboratory of a novel role of megakaryocytes (MKs) produced by the hematopoietic system in stimulating bone formation by osteoblasts (OBs);findings in the ..
  9. MICHAEL ALLAN HOLINSTAT; Fiscal Year: 2016
    ..will be addressed with physiology, biochemistry, genomic and cell biology approaches in human platelets and megakaryocytes. Aim 1 will dissect racial differences in platelet function using physiological and biochemical endpoints to ..
  10. Diane S Krause; Fiscal Year: 2016
    ..is focused on determining the basic molecular mechanisms underlying polyploidization and maturation of megakaryocytes, which are essential for effective platelet formation by adult megakaryocytes (Mk)...
  11. The role of VWF and platelets in BBB alterations associated with hypoxia
    GEORGETTE LEILA SUIDAN; Fiscal Year: 2013
    ..von Willebrand Factor (VWF) is a glycoprotein that is only synthesized by endothelial cells and megakaryocytes. While it is known that VWF is expressed abundantly by cerebral endothelial cells (CECs), very little is known ..
  12. Nikon A1RSI Confocal Microscope
    Sailen Barik; Fiscal Year: 2012
    ..mitochondria interaction;Regulation of innate immunity by RNA viruses;Differentiation of megakaryocytes and pluripotent stem cells;Small RNA biogenesis and function...
  13. In vivo lentiviral transduction of bone marrow cells for hemophilia gene therapy
    Carol H Miao; Fiscal Year: 2013
    ..whereas lentiviral vectors driven by a platelet-specific promoter will direct FVIII gene expression only in megakaryocytes and platelets...
  14. Gerd A Blobel; Fiscal Year: 2016
    ..model in which the FOG1-NuRD interaction is disrupted, we observed that in developing erythroid cells and megakaryocytes NuRD is required for both repression and activation of specific genes...
  15. Proteoglycan-4:A novel protein regulating skeletal actions of parathyroid hormone
    CHAD MICHAEL NOVINCE; Fiscal Year: 2010
    ..PTH signaling regulates the expression of genes which support both hematopoietic stem cells (HSCs) and megakaryocytes. Both HSCs and megakaryocytes are strong candidate regulators of PTH anabolic actions...
  16. Linzhao Cheng; Fiscal Year: 2015
    ..stem cells (iPS) from peripheral blood mononuclear cells, and then differentiate these stem cells into megakaryocytes (2) efficiently produce iPS and megakaryocytes using a novel pooling method, and (3) produce iPS and ..
  17. Dao Pan; Fiscal Year: 2016
    ..Moreover, we showed for the first time that megakaryocytes are capable of over-producing lysosomal enzymes and packaging them into platelets for cross-correction of ..
  18. K Vinod Vijayan; Fiscal Year: 2016
    ..Depletion of Gb1 in murine megakaryocytes or blockade of G[unreadable]? signaling in platelets, decreased thrombin receptor activating peptide induced ..
  19. Role of shear forces in proplatelet production from stem cells in bioreactors
    Eleftherios T Papoutsakis; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Megakaryocytes (Mks) are derived from hematopoietic stem cells...
  20. Elucidating mechanisms governing transcriptional regulation of the human LAT gene
    Timothy S Finco; Fiscal Year: 2013
    ..mammals, is critical for the development and/or function of T cells, mast cells, Natural Killer cells, and megakaryocytes/platelets...
  21. Zhe Li; Fiscal Year: 2015
    ..g., E2F targets, including Myc) in fetal megakaryocytes;(2) To test whether constitutively active IGF/IGF1R signaling cooperates with GATA1s in vitro and in vivo to ..
  22. Genetic analysis of stem cell maintenance in vivo
    Sean J Morrison; Fiscal Year: 2012
    ..Our preliminary expression data suggest that megakaryocytes are the major source of Ang-1 in the bone marrow and that there are multiple sources of SCF including both ..
  23. Integral role of hematopoietic cells in PTH actions in bone
    Laurie McCauley; Fiscal Year: 2009
    ..PTH has also been found to up regulate genes important in megakaryocyte differentiation and function. Megakaryocytes are intriguing osteoimmunomodulatory cells and valid candidates of PTH actions in the bone environment...
  24. Joseph E Italiano; Fiscal Year: 2016
    ..Although it is well established that platelets originate from megakaryocytes, many unanswered questions remain regarding the mechanics by which platelets are formed and released...
  25. The F-BAR protein CIP4 in WAS-dependent thrombocytopenia
    SETH JOEL COREY; Fiscal Year: 2012
    ..promotes platelet production and that a deficiency of either CIP4 or WASP perturbs actin polymerization in megakaryocytes, which results in defective proplatelet formation...
  26. The Biochemistry and Physiology of Platelet TFPI
    SUSAN ANTONE MARONEY; Fiscal Year: 2013
    ..The long term goal of our proposed studies is to understand the role of TFPI produced by megakaryocytes and expressed on the surface of activated platelets in controlling intravascular TF activity...
  27. Mortimer Poncz; Fiscal Year: 2016
    ..training opportunities in a wide variety of basic and clinical research areas including hemoglobinopathies, megakaryocytes and platelets...
  28. Mortimer Poncz; Fiscal Year: 2015
    ..be pursued simultaneously building on our preliminary data: 1) Enhance directed differentiation of hESCs into megakaryocytes (Megs) by improving the efficiency of hESC to hematopoietic mesoderm development and directing hematopoietic ..
  29. Stress and Platelet NPY in Vascular Remodeling
    John W Osborn; Fiscal Year: 2012
    ..we discovered that C57/BL mice, also used for pro- atherosclerotic ApoE-/- - do not express NPY in megakaryocytes (MK)/platelets and form mild or no lesions in response to angioplasty (neointima) and atherosclerosis (intimal ..
  30. Diagnostic Assay for Thrombocytosis
    Dmitri V Gnatenko; Fiscal Year: 2010
    ..distinct subtype of myeloproliferative disorders, thrombocytosis, characterized by increased proliferation of megakaryocytes and resultant elevated levels of circulating platelets...
  31. Robert Sackstein; Fiscal Year: 2016
    ..terminal lactosaminyl glycans;Project 3 (Hoffmeister) will study mouse and human megakaryocyte progenitors and megakaryocytes to define the temporal changes and function(s) of terminal lactosaminyl glycans during thrombopoiesis, and ..
  32. Immunoregulatory responses in patients with ITP
    Karina Yazdanbakhsh; Fiscal Year: 2012
    ..Damage to megakaryocytes resulting in an inflammatory marrow environment and elevated circulatory pro-inflammatory cytokines have been ..
  33. Development of a novel small molecule, UTL-5g, to treat oxaliplatin-induced throm
    Jiajiu Shaw; Fiscal Year: 2013
    ..all these studies, when applicable, we will conduct counts/analyses on platelets, WBC, bone marrow and CD41+ megakaryocytes. We will also monitor the injuries on liver and kidney by analyzing AST, ALT, BUN, and creatine...
  34. MASTL kinase activity in megakaryocyte differentiation
    HELEN JANETTE JOHNSON; Fiscal Year: 2010
    ..microtubule associated serine/threonine kinase-like molecule, MASTL regulates terminal differentiation of megakaryocytes, as well as to provide the applicant, Dr...
  35. MKL in megakaryocytopoiesis
    Diane S Krause; Fiscal Year: 2013
    ..megakaryoblasts, which undergo endomitosis to become polyploid, and subsequently undergo maturation to mature megakaryocytes that can release platelets into the circulation...
  36. The Biological Roles of Phoshadylinositol Transfer Proteins in Platelets
    Charles S Abrams; Fiscal Year: 2013
    ..These mice have platelets and mature megakaryocytes lacking either PITP1 or PITP2, but they have normal expression of these proteins in all other tissues...
  37. James Palis; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Platelets are anucleate cells derived from megakaryocytes (megs) that serve as critical components of hemostasis and thrombus formation, and mediate aspects of inflammation, immunity, and angiogenesis...
  38. MRP-14 and Cardiovascular Disease
    Daniel I Simon; Fiscal Year: 2010
    ..Generated from cytoplasmic extensions from megakaryocytes, platelets retain megakaryocyte-derived mRNAs...
  39. Reverse Transcriptase Activity in Megakaryocytes and Platelets
    ANDREW SCOTT WEYRICH; Fiscal Year: 2010
    ..functional spliceosome demonstrates remarkable specialization and intricate information transfer from parental megakaryocytes to terminally differentiated platelets...
  40. 2013 Cell Biology of Megakaryocytes and Platelets GRC &GRS
    Katya Ravid; Fiscal Year: 2013
    ..The Gordon Research Conference (GRC) on the Cell Biology of Megakaryocytes and Platelets is the premier scientific meeting focused on the biology of megakaryocytes (MKs) and the ..
  41. John D Crispino; Fiscal Year: 2016
    ..proliferate to a limited extent and then give rise to small numbers of differentiated and polyploid megakaryocytes. However, upon acquisition of mutations in key signaling molecules, such as MPL or JAK2, megakaryocyte ..
  42. Martha C Sola-Visner; Fiscal Year: 2015
    ..are not understood, but are clearly related to the unique biological characteristics of fetal/neonatal megakaryocytes (MKs)...
  43. Katya Ravid; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): Megakaryocytes (MKs) are responsible for the production of platelets, which have a major impact on blood homeostasis...
  44. A(1-7)-Mediated Mitigation of Radiation Induced Thrombocytopenia
    Kathleen E Rodgers; Fiscal Year: 2010
    ..Further, the effect of A(1-7) administration on the number of megakaryocyte progenitors and megakaryocytes (number and ploidy) after in intact and angiotensin receptor (including MAS) knock out mice will be determined...
  45. Sanford J Shattil; Fiscal Year: 2015
    ..and how ADAP interacts with such integrin-proximal regulators in platelets, in gene-targeted primary murine megakaryocytes, and in model cells engineered to recapitulate [unreadable]IIb[unreadable]3 activation...
  46. ROLE OF STATHMIN IN MEGAKARYOPOIESIS AND PLATELET PRODUCTION
    CAMELIA IANCURUBIN; Fiscal Year: 2010
    ..Megakaryopoiesis is a complex process in which bone marrow megakaryocytes give rise to circulating platelets...
  47. The mechanism and clinical implications of the negative paracrine effect of PF4
    Michele P Lambert; Fiscal Year: 2012
    ..Using murine models, I have demonstrated that platelet factor 4 (PF4), which is synthesized in developing megakaryocytes, is released from these cells and behaves as a negative paracrine, especially in clinical settings associate ..
  48. THROMBOPOIETIN: IMMUNOASSAY AND CHARACTERIZATION
    TED MC DONALD; Fiscal Year: 1993
    ..efficacy of TSF in bone marrow suppressed animals, 5) develop a radioimmunoassay for TSF, 6) measure ploidy of megakaryocytes in animals after TSF treatment, 7) establish TSF combining sites on megakaryocytes, 8) clarify effects of ..
  49. EDWARD FRANKLIN PLOW; Fiscal Year: 2016
    ..Aim 3 emphasizes the effects of the kindlins on integrin-mediated responses in intact cells, platelets, megakaryocytes and endothelial cells...
  50. Effect of MKL1 on murine embryonic megakaryocytopoiesis
    ELENOE C SMITH; Fiscal Year: 2010
    Acute Megakaryoblastic Leukemia is characterized by the blocked differentiation and improper proliferation of megakaryocytes. The 1;22 chromosomal translocation that has been found to associate with AMKL infants implicates the fusion ..
  51. EFFECTS OF POLYUNSATURATED FATTY ACIDS ON MEGAKARYOCYTES
    PAUL SCHICK; Fiscal Year: 1991
    Our hypothesis is that polyunsaturated fatty acid (PUFA) enriched diets have a major action on megakaryocytes. The megakaryocyte is a bone marrow cell whose primary function is to synthesize platelets, and the platelet itself has little ..
  52. BIOLOGIC AND IMMUNOLOGIC ASPECTS OF TRANSFUSION MEDICINE
    Sherrill Slichter; Fiscal Year: 2009
    ..Dr. Gilligan and Reems'project expects to identify the optimal methods of growing megakaryocytes in culture with the goal of producing platelets or "platelet-like fragments" that function similarly to ..
  53. Megakaryocyte Chemokines & Post-Irradiation Thrombocytopenia
    Mortimer Poncz; Fiscal Year: 2009
    ..We found that at least one chemokine that is released by developing megakaryocytes, platelet factor 4 (PF4), acts via a negative paracrine loop to inhibit new megakaryocyte formation and to ..
  54. Bipotential lineage determination by EKLF
    James J Bieker; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Megakaryocytes and erythroid cells are thought to derive from a common progenitor during hematopoietic differentiation...
  55. BIOSYNTHESIS AND GENETICS OF GLYCOPROTEINS IIB AND IIIA
    Marc Shuman; Fiscal Year: 1993
    ..In addition, possible abnormalities in mRNA will be analyzed in platelets and megakaryocytes by: i) the polymerase chain reaction using Taq polymerase and oligonucleotide primers based on known GPIIb-..
  56. Processed Defining Megakaryocyte Endocytosis of Factor V
    PAULA TRACY; Fiscal Year: 2005
    ..factor V originates from plasma through endocytosis of plasma factor V by platelet progenitor cells, megakaryocytes. However, platelet-derived factor Va exhibits biochemical and physical differences that clearly distinguish it ..
  57. John H Hartwig; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Platelets are subcellular particles produced by megakaryocytes that circulate in blood...
  58. STUDIES OF MEGAKARYOCYTOPOIESIS
    Samuel Burstein; Fiscal Year: 1991
    ..specificity, promotes both the proliferation of the megakaryocytic progenitor cell and the differentiation of megakaryocytes in vitro...
  59. Proteomic Study of Megakaryocyte Transcriptional Control
    Alan Cantor; Fiscal Year: 2007
    b>Megakaryocytes are large polyploid bone marrow cells that play essential roles in hemostasis through the generation of platelets...
  60. MARROW TRANSPLANT THERAPY FOR RETROVIRUS INFECTIONS
    PETER GASPER; Fiscal Year: 1992
    ..are hemolymphatic cell infections--FeLV replication occurs primarily in mitotically active myelopoietic cells, megakaryocytes and follicular lymphoblasts in lymphatic tissues...
  61. Defining the Role of TREM-Like Transcript-1 in Platelet Aggregation
    A Washington; Fiscal Year: 2009
    ..TLT-1 is abundant, specific to platelets and megakaryocytes, and up-regulated from the alpha-granules upon stimulation with thrombin or LPS to the platelet surface...
  62. Defining the Role of TREM-Like Transcript-1 in Platelet Aggregation
    A Washington; Fiscal Year: 2007
    ..TLT-1 is abundant, specific to platelets and megakaryocytes, and up-regulated from the alpha-granules upon stimulation with thrombin or LPS to the platelet surface...
  63. REGULATION OF HUMAN MEGAKARYOCYTOPOIESIS
    Alan Gewirtz; Fiscal Year: 1992
    ..Aim #2 will be to examine the effect of mature megakaryocytes and platelets, or their constituents/products, on the growth of CFU-MEG in culture...