Thrombopoietin Induces Megakaryocyte Differentiation in Hematopoietic Progenitor FDC-P2 Cells (∗)

• Published in: The Journal of biological chemistry Vol. 270; no. 34; pp. 19673 - 19675
• Main Authors: Nagata, Yuka, Nagahisa, Hiroshi, Aida, Yoko, Okutomi, Keiichi, Nagasawa, Toshiro, Todokoro, Kazuo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.08.1995; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Antigens, Differentiation - biosynthesis; Cell Differentiation - drug effects; Cell Division - drug effects; Cell Line; DNA-Binding Proteins - biosynthesis; Erythroid-Specific DNA-Binding Factors; GATA1 Transcription Factor; Hematopoiesis - drug effects; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Megakaryocytes - cytology; Megakaryocytes - drug effects; Megakaryocytes - metabolism; Mice; Neoplasm Proteins; NF-E2 Transcription Factor; NF-E2 Transcription Factor, p45 Subunit; Platelet Membrane Glycoproteins - biosynthesis; Proto-Oncogene Proteins - drug effects; Receptors, Cytokine; Receptors, Immunologic - drug effects; Receptors, Thrombopoietin; Thrombopoietin - pharmacology; Transcription Factors - biosynthesis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.34.19673

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.