Hes1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation.
Immunity
; 33(5): 671-84, 2010 Nov 24.
Article
en En
| MEDLINE
| ID: mdl-21093323
ABSTRACT
Although canonical Notch signaling regulates multiple hematopoietic lineage decisions including T cell and marginal zone B cell fate specification, the downstream molecular mediators of Notch function are largely unknown. We showed here that conditional inactivation of Hes1, a well-characterized Notch target gene, in adult murine bone marrow (BM) cells severely impaired T cell development without affecting other Notch-dependent hematopoietic lineages such as marginal zone B cells. Competitive mixed BM chimeras, intrathymic transfer experiments, and in vitro culture of BM progenitors on Delta-like-expressing stromal cells further demonstrated that Hes1 is required for T cell lineage commitment, but dispensable for Notch-dependent thymocyte maturation through and beyond the beta selection checkpoint. Furthermore, our data strongly suggest that Hes1 is essential for the development and maintenance of Notch-induced T cell acute lymphoblastic leukemia. Collectively, our studies identify Hes1 as a critical but context-dependent mediator of canonical Notch signaling in the hematopoietic system.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Activación de Linfocitos
/
Proteínas de Homeodominio
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Receptores Notch
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Suiza