GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages

Hiromi Iwasaki, Shin Ichi Mizuno, Richard A. Wells, Alan B. Cantor, Sumiko Watanabe, Koichi Akashi

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

GATA-1 is an essential transcription factor for megakaryocyte and erythrocyte (MegE) development. Here we show that hematopoietic progenitors can be reprogrammed by the instructive action of GATA-1. Enforced expression of GATA-1 in hematopoietic stem cells led to loss of self-renewal activity and the exclusive generation of MegE lineages. Strikingly, ectopic GATA-1 reprogrammed common lymphoid progenitors as well as granulocyte/monocyte (GM) progenitors to differentiate into MegE lineages, while inhibiting normal lymphoid or GM differentiation. GATA-1 upregulated critical MegE-related transcription factors such as FOG-1 and GATA-2 in lymphoid and GM progenitors, and their MegE development did not require "permissive" erythropoietin signals. Furthermore, GATA-1 induced apoptosis of proB and myelomonocytic cells, which could not be prevented by enforced permissive Bcl-2 or myeloid cytokine signals. Thus, GATA-1 specifically instructs MegE commitment while excluding other fate outcomes in stem and progenitor cells, suggesting that regulation of GATA-1 is critical in maintaining multilineage homeostasis.

Original languageEnglish
Pages (from-to)451-462
Number of pages12
JournalImmunity
Volume19
Issue number3
DOIs
Publication statusPublished - Sep 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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