GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages.
Immunity
; 19(3): 451-62, 2003 Sep.
Article
en En
| MEDLINE
| ID: mdl-14499119
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Megacariocitos
/
Diferenciación Celular
/
Células Progenitoras Mieloides
/
Proteínas de Unión al ADN
/
Eritrocitos
Límite:
Animals
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos