Thrombopoiesis
Mary K. Boudreaux
Search for more papers by this authorPete W. Christopherson
Search for more papers by this authorMary K. Boudreaux
Search for more papers by this authorPete W. Christopherson
Search for more papers by this authorMarjory B. Brooks DVM, DACVIM
Director, Comparative Coagulation Section
Animal Health Diagnostic Center, Cornell University, Ithaca, New York, USA
Search for more papers by this authorKendal E. Harr DVM, MS, DACVP
URIKA, LLC, Mukilteo, Washington, USA
Search for more papers by this authorDavis M. Seelig DVM, PhD, DACVP
Associate Professor, Clinical Pathology
Department of Veterinary Clinical Sciences, University of Minnesota, College of Veterinary Medicine, St. Paul, Minnesota, USA
Search for more papers by this authorK. Jane Wardrop DVM, MS, DACVP
Professor and Director, Clinical Pathology Laboratory
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA
Search for more papers by this authorDouglas J. Weiss DVM, PhD, DACVP
Emeritus Professor
College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA
Search for more papers by this authorSummary
Megakaryocytes are derived from a bipotent megakaryocyte–erythroid progenitor. Transendothelial migration and proplatelet formation and release are dependent on the interaction of megakaryocytes with bone marrow endothelial cells via adhesion molecules, including vascular cell adhesion molecule-1 and integrin α 4 β 1 . Several transcription factors determined to be critical for thrombopoiesis in humans and mice likely play a similar regulatory role in other species. In humans and domestic animals, megakaryocytes are located primarily in bone marrow. Megakaryocytes undergo some degree of fragmentation in the pulmonary circulation in most mammalian species. There are four to five times more megakaryocytes in mouse bone marrow than in human bone marrow, and mouse megakaryocytes are smaller. Megakaryocyte ploidy is not consistently related to platelet mass and platelet mass is not constant across species. In dogs and cats, platelet size is inversely proportional to platelet number, whereas there is no correlation between platelet number and size in cows, goats, or ponies.
REFERENCES
- Akashi K , Traver D , Miyamoto T , et al. Clonogenic common myeloid progenitor that gives rise to all myeloid lineages . Nature 2000 ; 404 : 193 – 197 .
- Alexander WS , Roberts AW , Nicola NA , et al. Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacing the thrombopoietic receptor c-Mpl . Blood 1996 ; 87 : 2162 – 2170 .
- Bartley TD , Bogenberger J , Hunt P , et al. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl . Cell 1994 ; 77 : 1117 – 1124 .
- Boudreaux MK , Ebbe S. Comparison of platelet number, mean platelet volume and platelet mass in five mammalian species . Comp Haematol Intl 1998 ; 8 : 16 – 20 .
- Crispino JD . GATA1 in normal and malignant hematopoiesis . Semin Cell Dev Biol 2005 ; 6 : 137 – 147 .
- Davis B , Toivio-Kinnucan M , Schuller S , et al. Mutation in β1-tubulin correlates with the macrothrombocytopenia of Cavalier King Charles Spaniels . J Vet Intern Med 2008 ; 22 : 540 – 545 .
- Debili N , Coulombel L , Croisille L , et al. Characterization of a bipotent erythro-megakaryocytic progenitor in human bone marrow . Blood 1996 ; 88 : 1284 – 1296 .
- Ebbe S , Boudreaux MK . Relationship of megakaryocyte ploidy with platelet number and size in cats, dogs, rabbits, and mice . Comp Haematol Intl 1998 ; 8 : 21 – 25 .
- Freson K , Matthijs G , Thys C , et al. Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation . Human Mol Genet 2002 ; 11 : 147 – 152 .
- Gelain ME , Bertazzolo W , Tutino G , et al. A novel point mutation in the β1-tubulin gene in asymptomatic macrothrombocytopenic Norfolk and Cairn Terriers . Vet Clin Pathol 2014 ; 43 : 317 – 321 .
- Grozovsky R , Giannini S , Falet H , et al. Regulating billions of blood platelets: glycans and beyond . Blood 2015 ; 126 : 1877 – 1884 .
- Gurney AL , Kuang WJ , Xie MH , et al. Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin . Blood 1995 ; 85 : 981 – 988 .
- Hoffmeister KM , Falet H . Platelet clearance by the hepatic Ashwell-Morrell receptor: mechanisms and biological significance . Thromb Res 2016 ; 141 ( Suppl 2 ): S68 – S72 .
- Iancu-Rubin C , Nasrallah CA , Atweh GF . Stathmin prevents the transition from a normal to an endomitotic cell cycle during megakaryocyte differentiation . Cell Cycle 2005 ; 4 : 1774 – 1782 .
- Junt T , Schulze H , Chen Z , et al. Dynamic visualization of thrombopoiesis within bone marrow . Science 2007 ; 317 : 1767 – 1770 .
- Kaser A , Brandacher G , Steurer W , et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis . Blood 2001 ; 98 : 2720 – 2725 .
- Kato T , Matsumoto A , Ogami K , et al. Native thrombopoietin: structure and function . Stem Cell 1998 ; 16 : 322 – 328 .
- Kaushansky K . Historical review: megakaryopoiesis and thrombopoiesis . Blood 2008 ; 111 : 981 – 986 .
- Lok S , Kaushansky K , Holly RD , et al. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo . Nature 1994 ; 369 : 565 – 568 .
- Matsushiro H , Kato H , Tahara T , et al. Molecular cloning and functional expression of feline thrombopoietin . Vet Immunol Immunopathol 1998 ; 66 : 225 – 236 .
- Michaud J , Wu F , Osato M , et al. In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis . Blood 2002 ; 99 : 1364 – 1373 .
- Münzer , P , Walker-Allgaier , B , Geue S , et al. CK2β regulates thrombopoiesis and Ca 2+ -triggered platelet activation in arterial thrombosis . Blood 2017 ; 130 : 2774 – 2785 .
- Nishimura S , Nagasaki M , Kunishima S , et al. IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs . J Cell Biol 2015 ; 209 : 453 – 466 .
- Richardson JL , Shivdasani RA , Boers C , et al. Mechanisms of organelle transport and capture along proplatelets during platelet production . Blood 2005 ; 106 : 4066 – 4075 .
- Rohatgi R , Ma L , Miki H , et al. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly . Cell 1999 ; 97 : 221 – 231 .
- Rosmarin AG , Resendes KK , Yang Z , et al. GA-binding protein transcription factor: a review of GABP as an integrator of intracellular signaling and protein-protein interactions . Blood Cell Mol Dis 2004 ; 32 : 143 – 154 .
- Schulze H , Korpal M , Hurov J , et al. Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis . Blood 2006 ; 107 : 3868 – 3875
- Shiraga M , Ritchie A , Aidoudi A , et al. Primary megakaryocytes reveal a role for transcription factor NF-E2 in integrin alpha IIb beta 3 signaling . J Cell Biol 1999 ; 147 : 1419 – 1430 .
- Stachura DL , Chou ST , Weiss MJ . Early block to erythromegakaryocytic development conferred by loss of transcription factor GATA1 . Blood 2006 ; 107 : 87 – 97 .
- Stegner D , vanEeuwijk JMM , Angay O , et al. Thrombopoiesis is spatially regulated by the bone marrow vasculature . Nat Commun 2017 ; 8 : 1 – 11 .
- Sun L , Mao G , Rao AK . Association of CBFA2 mutation with decreased platelet PKC-theta and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation . Blood 2004 ; 103 : 948 – 954 .
- Takakura N , Watanabe T , Suenobu S , et al. A role for hematopoietic stem cells in promoting angiogenesis . Cell 2000 ; 102 : 199 – 209 .
- Tober J , Koniski A , McGrath KE , et al. The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis . Blood 2007 ; 109 : 1433 – 1441 .
- Topp KS , Tablin T , Levin J . Culture of isolated bovine megakaryocytes on reconstituted basement membrane matrix leads to proplatelet process formation . Blood 1990 ; 76 : 912 – 924 .
- Tsai FY , Keller G , Kuo FC , et al. An early haematopoietic defect in mice lacking the transcription factor GATA2 . Nature 1994 ; 371 : 221 – 226 .
- Varghese LN , Defour JP , Pecquet C , et al. The thrombopoietin receptor: structural basis of traffic and activation by ligand, mutations, agonists, and mutated calreticulin . Front Endocrinol (Lausanne) 2017 ; 8 : 1 – 13 .
- Vitrat N , Cohen-Solal K , Pique C , et al. Endomitosis of human megakaryocytes are due to abortive mitosis . Blood 1998 ; 91 : 3711 – 3723 .
- Wendling F , Vigon I , Souyri M , et al. Myeloid progenitor cells transformed by the myeloproliferative leukemia virus proliferate and differentiate in vitro without addition of growth factors . Leukemia 1989 ; 3 : 475 – 480 .
- Wu C . PINCH, N(i)ck and the ILK: network wiring at cell-matrix adhesions . Trends Cell Biol 2005 ; 15 : 460 – 466 .
- Zhang J , Zhuang R , Zhang X , et al. CD226 is involved win megakaryocyte activation and early-stage differentiation . Mol Immunol 2019 ; 107 : 123 – 131 .
