Erythropoietin-dependent induction of hemoglobin synthesis in a cytokine-dependent cell line M-TAT

Naoko Minegishi, Masayoshi Minegishi, Shigeru Tsuchiya, Hiromi Fujie, Tadashi Nagai, Norio Hayashi, Masayuki Yamamoto, Tasuke Konno

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

M-TAT is a cytokine-dependent cell line with the potential to differentiate along the erythroid and megakaryocytic lineages. We cultured M-TAT cells long term (>1 year) in the continuous presence of erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), or stem cell factor (SCF). These long term cultures are referred to as M-TAT/EPO, M-TAT/GM-CSF, and M-TAT/SCF cells, respectively. Hemoglobin concentration and γ-globin and erythroid δ-aminolevulinate synthase mRNA levels were significantly higher in M-TAT/EPO cells than in M-TAT/GM-CSF cells. When the supplemented cytokine was switched from GM-CSF to EPO, hemoglobin synthesis in M-TAT/GM-CSF cells increased rapidly (within 5 h), and the level of GATA-1 mRNA increased. In contrast, the addition of GM-CSF to the M-TAT/EPO cell culture decreased the amount of hemoglobin, even in the presence of EPO, indicating that the EPO signal for erythroid differentiation is suppressed by GM-CSF. Thus, erythroid development of M-TAT cells is promoted by EPO and suppressed by GM-CSF. These results support the hypothesis that EPO actively influences the programming of gene expression required for erythroid progenitor cell differentiation.

Original languageEnglish
Pages (from-to)27700-27704
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number44
Publication statusPublished - 1994 Nov 4

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