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

Immunity. 2003 Sep;19(3):451-62. doi: 10.1016/s1074-7613(03)00242-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Carrier Proteins / metabolism
  • Cell Differentiation / physiology*
  • DNA-Binding Proteins / metabolism*
  • Erythrocytes / metabolism*
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Megakaryocytes / metabolism*
  • Mice
  • Mice, Transgenic
  • Myeloid Progenitor Cells / metabolism*
  • Nuclear Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / physiology
  • Transcription Factors / metabolism*


  • Carrier Proteins
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factors
  • Zfpm1 protein, mouse
  • Granulocyte-Macrophage Colony-Stimulating Factor