PLATELET FORMATION

Thrombocytopenia is the underlying cause of a number of major clinical conditions and genetic disorders worldwide. While therapeutic agents that bind and stimulate the thrombopoietin receptor are currently available, the development of drugs that directly stimulate megakaryocytes to generate platelets has lagged behind. To improve the management of thrombocytopenia, we will need to define the cell biological pathways that drive the production of platelets from megakaryocytes. This review integrates the latest research of platelet biogenesis and focuses on the molecular pathways that power and regulate proplatelet production.

[1]  A. Ritchie,et al.  Primary Megakaryocytes Reveal a Role for Transcription Factor Nf-E2 in Integrin αiibβ3 Signaling , 1999, The Journal of cell biology.

[2]  M. Hokom,et al.  Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. , 1995, Blood.

[3]  W. Vainchenker,et al.  Differential regulation of actin stress fiber assembly and proplatelet formation by alpha2beta1 integrin and GPVI in human megakaryocytes. , 2004, Blood.

[4]  J. Hartwig,et al.  Blood Platelets Are Assembled Principally at the Ends of Proplatelet Processes Produced by Differentiated Megakaryocytes , 1999, The Journal of cell biology.

[5]  A. Balduini,et al.  Megakaryocytes of patients with MYH9-related thrombocytopenia present an altered proplatelet formation , 2009, Thrombosis and Haemostasis.

[6]  P. Vyas,et al.  Mice lacking transcription factor NF-E2 provide in vivo validation of the proplatelet model of thrombocytopoiesis and show a platelet production defect that is intrinsic to megakaryocytes. , 1998, Blood.

[7]  W. Vainchenker,et al.  Ultrastructure of platelet formation by human megakaryocytes cultured with the Mpl ligand. , 1997, Blood.

[8]  N. Debili,et al.  Of mice and men: comparison of the ultrastructure of megakaryocytes and platelets. , 2001, Experimental hematology.

[9]  Joseph E Italiano,et al.  Dynamic Visualization of Thrombopoiesis Within Bone Marrow , 2007, Science.

[10]  J. Hartwig,et al.  A lineage-restricted and divergent β-tubulin isoform is essential for the biogenesis, structure and function of blood platelets , 2001, Current Biology.

[11]  S. Israels,et al.  Platelet dense granules: structure, function and implications for haemostasis. , 1999, Thrombosis research.

[12]  R. Hynes,et al.  Hemostasis in the Mouse (Mus musculus): A Review , 1999, Thrombosis and Haemostasis.

[13]  A. Leavitt,et al.  Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. Ingber,et al.  The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway. , 2007, Blood.

[15]  W. Piacibello,et al.  In vitro and in vivo megakaryocyte differentiation of fresh and ex-vivo expanded cord blood cells: rapid and transient megakaryocyte reconstitution. , 2003, Haematologica.

[16]  S. Orkin,et al.  Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoeitin/MGDF in megakaryocyte development , 1995, Cell.

[17]  T. Kamata,et al.  Megakaryocytes derived from human embryonic stem cells: a genetically tractable system to study megakaryocytopoiesis and integrin function , 2005, Journal of thrombosis and haemostasis : JTH.

[18]  R. Shivdasani.  Molecular and Transcriptional Regulation of Megakaryocyte Differentiation , 2001, Stem cells.

[19]  A. Nurden.  Qualitative disorders of platelets and megakaryocytes , 2005, Journal of thrombosis and haemostasis : JTH.

[20]  F. Tablin,et al.  Blood platelet formation in vitro. The role of the cytoskeleton in megakaryocyte fragmentation. , 1990, Journal of cell science.

[21]  Linheng Li,et al.  The stem cell niches in bone. , 2006, The Journal of clinical investigation.

[22]  R. Lemieux,et al.  Preferential ex vivo expansion of megakaryocytes from human cord blood CD34+-enriched cells in the presence of thrombopoietin and limiting amounts of stem cell factor and Flt-3 ligand. , 2003, Journal of hematotherapy & stem cell research.

[23]  David N. Haylock,et al.  Ex vivo expansion and maturation of peripheral blood CD34+ cells into the myeloid lineage. , 1992 .

[24]  S. Watson,et al.  A product of their environment: Do megakaryocytes rely on extracellular cues for proplatelet formation? , 2006, Platelets.

[25]  Joseph E Italiano,et al.  Mechanisms of organelle transport and capture along proplatelets during platelet production. , 2005, Blood.

[26]  S. Watson,et al.  Regulation of proplatelet formation and platelet release by integrin alpha IIb beta3. , 2006, Blood.

[27]  R. Flaumenhaft,et al.  Platelet alpha-granules: basic biology and clinical correlates. , 2009, Blood reviews.

[28]  R. Shivdasani,et al.  The microtubule modulator RanBP10 plays a critical role in regulation of platelet discoid shape and degranulation. , 2009, Blood.

[29]  J. Hartwig,et al.  Cytoskeletal mechanisms for platelet production. , 2006, Blood cells, molecules & diseases.

[30]  T. Farver,et al.  Circulating proplatelets: isolation and quantitation in healthy rats and in rats with induced acute blood loss. , 1987, American journal of veterinary research.

[31]  A. Balduini,et al.  Adhesive receptors, extracellular proteins and myosin IIA orchestrate proplatelet formation by human megakaryocytes , 2008, Journal of thrombosis and haemostasis : JTH.

[32]  D. Baruch,et al.  Exposure of human megakaryocytes to high shear rates accelerates platelet production. , 2009, Blood.

[33]  S. Jackson,et al.  Glycoprotein (GP) Ib-IX-transfected Cells Roll on a von Willebrand Factor Matrix under Flow , 1999, The Journal of Biological Chemistry.

[34]  M. Korpal,et al.  RanBP10 Is a Cytoplasmic Guanine Nucleotide Exchange Factor That Modulates Noncentrosomal Microtubules* , 2008, Journal of Biological Chemistry.