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Shaping of terminal megakaryocyte differentiation and proplatelet development by sphingosine-1-phosphate receptor S1P4

Item Type:Article
Title:Shaping of terminal megakaryocyte differentiation and proplatelet development by sphingosine-1-phosphate receptor S1P4
Creators Name:Golfier, S. and Kondo, S. and Schulze, T. and Takeuchi, T. and Vassileva, G. and Achtman, A.H. and Graeler, M.H. and Abbondanzo, S.J. and Wiekowski, M. and Kremmer, E. and Endo, Y. and Lira, S.A. and Bacon, K.B. and Lipp, M.
Abstract:Megakaryocytes, which mature from hematopoietic progenitors in the bone marrow, further differentiate by reorganizing their cytoplasm into long proplatelet extensions that release platelets into the circulation. The molecular mechanisms underlying this highly dynamic cytoplasmic and cytoskeletal remodeling process are only poorly understood. Here we report that sphingosine 1-phosphate receptor 4 (S1P4) is specifically up-regulated during the development of human megakaryocytes from progenitor cells and is expressed in mature murine megakaryocytes. Megakaryocytes generated from S1P4-deficient murine bone marrow showed atypical and reduced formation of proplatelets in vitro. The recovery of platelet numbers after experimental thrombocytopenia was significantly delayed in S1p4(-/-) mice. Remarkably, overexpression and stimulation of S1P4 in human erythroleukemia HEL cells promoted endomitosis, formation of cytoplasmic extensions, and subsequent release of platelet-like particles. These observations indicate that S1P4 is involved in shaping the terminal differentiation of megakaryocytes.
Keywords:Platelets, Lysophospholipids, Receptor-Deficient Mice, Animals, Mice
Source:FASEB Journal
ISSN:0892-6638
Publisher:Federation of American Societies for Experimental Biology (U.S.A.)
Volume:24
Number:12
Page Range:4701-4710
Date:December 2010
Official Publication:https://doi.org/10.1096/fj.09-141473
PubMed:View item in PubMed

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