TY - JOUR
T1 - GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages
AU - Iwasaki, Hiromi
AU - Mizuno, Shin Ichi
AU - Wells, Richard A.
AU - Cantor, Alan B.
AU - Watanabe, Sumiko
AU - Akashi, Koichi
N1 - Funding Information:
We thank M.A. Handley for technical assistance with flow cytometry and D.J. Traver for critically reviewing the manuscript. We also thank J. Domen and I.L. Weissman for providing H-2k-Bcl-2 transgenic mice. This work was supported in part by grants from NIH (DK050654, DK061320, and CA072009), Damon-Runyon Cancer Research, and the Claudia Adams Barr Program to K.A. and by the Uehara Memorial Foundation to S.M.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S1074-7613(03)00242-5
DO - 10.1016/S1074-7613(03)00242-5
M3 - Article
C2 - 14499119
AN - SCOPUS:0141455931
VL - 19
SP - 451
EP - 462
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -
