Thrombopoietin induces megakaryocyte differentiation in hematopoietic progenitor FDC-P2 cells.
Thrombopoietin (Tpo) is a cytokine that specifically regulates megakaryocyte maturation and platelet production. Little is known about the molecular and cellular mechanism of the Tpo-induced megakaryocyte maturation process including polyploidization and platelet release. To study Tpo-induced megakaryocyte differentiation, a mouse cell line FD-TPO, which responds and grows with Tpo, was established from a interleukin-3-dependent hematopoietic progenitor cell line FDC-P2. The FD-TPO cells, expressing endogenous Tpo receptor, grew with Tpo in a dose-dependent manner. Further, Tpo stimulation dramatically induced expression of megakaryocyte/erythroid-specific transcription factors GATA-1 and NF-E2 in FD-TPO cells. Flow cytometry analysis demonstrated that expression of platelet-specific cell surface antigens including CD61 (GPIIIa) dramatically increased in Tpo-stimulated FD-TPO cells and that expression of myeloid-specific antigens, Gr-1 and Mac-1, decreased. Therefore, we concluded that the binding of Tpo to FD-TPO cells induces not only cell growth but also differentiation into mature megakaryocyte-like cells, and thus this cell line was found to be useful for the study of Tpo receptor-mediated growth and differentiation signals.
Nagata
Y
Y
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Nagahisa
H
H
Aida
Y
Y
Okutomi
K
K
Nagasawa
T
T
Todokoro
K
K
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D009363:Neoplasm Proteins; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000187:drug effects; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000187:drug effects; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D009363:Neoplasm Proteins; C494693:Nfe2 protein, mouse; D010980:Platelet Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; D014157:Transcription Factors; C082218:MPL protein, human; D013926:Thrombopoietin