Graded levels of GATA-1 expression modulate survival, proliferation, and differentiation of erythroid progenitors

Xiaoqing Pan, Osamu Ohneda, Kinuko Ohneda, Fokke Lindeboom, Fumiko Iwata, Ritsuko Shimizu, Masumi Nagano, Naruyoshi Suwabe, Sjaak Philipsen, Kim Chew Lim, James D. Engel, Masayuki Yamamoto

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Transcription factor GATA-1 plays an important role in gene regulation during the development of erythroid cells. Several reports suggest that GATA-1 plays multiple roles in survival, proliferation, and differentiation of erythroid cells. However, little is known about the relationship between the level of GATA-1 expression and its nature of multifunction to affect erythroid cell fate. To address this issue, we developed in vitro embryonic stem (ES) culture system by using OP9 stromal cells (OP9/ES cell co-culture system), and cultured the mutant (GATA-1.05 and GATA-1-null) and wild type (WT) ES cells, respectively. By using this OP9/ES cell co-culture system, primitive and definitive erythroid cells were developed individually, and we examined how expression level of GATA-1 affects the development of erythroid cells. GATA-1.05 ES-derived definitive erythroid cells were immature with the appearance of proerythroblasts, and highly proliferated, compared with WT and GATA-1-null ES-derived erythroid cells. Extensive studies of cell cycle kinetics revealed that the GATA-1.05 proerythroblasts accumulated in S phase and expressed lower levels of p16INK4A than WT ES cell-derived proerythroblasts. We concluded that GATA-1 must achieve a critical threshold activity to achieve selective activation of specific target genes, thereby influencing the developmental decision of an erythroid progenitor cell to undergo apoptosis, proliferation, or terminal differentiation.

Original languageEnglish
Pages (from-to)22385-22394
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number23
DOIs
Publication statusPublished - 2005 Jun 10
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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