Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling.
Dev Cell
; 18(4): 569-78, 2010 Apr 20.
Article
en En
| MEDLINE
| ID: mdl-20412772
ABSTRACT
The regulation of stem cell ontogeny is poorly understood. We show that the leukemia-associated Ets transcription factor, Tel1/ETV6, specifies the first hematopoietic stem cells (HSCs) in the dorsal aorta (DA). In contrast, Tel1/ETV6 has little effect on embryonic blood formation, further distinguishing the programming of the long- and short-term blood populations. Consistent with the notion of concordance of arterial and HSC programs, we show that Tel1/ETV6 is also required for the specification of the DA as an artery. We further show that Tel1/ETV6 acts by regulating the transcription of VegfA in both the lateral plate mesoderm and also in the somites. Exogenous VEGFA rescues Tel1/ETV6 morphants, and depletion of VEGFA or its receptor, Flk1, largely phenocopies Tel1/ETV6 depletion. Few such links between intrinsic and extrinsic programming of stem cells have been reported previously. Our data place Tel1/ETV6 at the apex of the genetic regulatory cascade leading to HSC production.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
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Células Sanguíneas
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Células Madre Hematopoyéticas
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Regulación del Desarrollo de la Expresión Génica
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Factor A de Crecimiento Endotelial Vascular
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Proteínas Proto-Oncogénicas c-ets
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2010
Tipo del documento:
Article