SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-ß signaling.
J Exp Med
; 215(5): 1337-1347, 2018 05 07.
Article
em En
| MEDLINE
| ID: mdl-29669741
ABSTRACT
Cell cycle quiescence is critical for hematopoietic stem cell (HSC) maintenance. TGF-ß signaling in bone marrow niche has been identified in regulating HSC quiescence; however, the intrinsic regulatory mechanisms remain unclear. This study reports that Shp-1 knockout HSCs have attenuated quiescence and impaired long-term self-renewal. SHP-1-activated HSCs are surrounded by megakaryocytes, which regulate HSC quiescence by producing TGF-ß1. Mechanistically, SHP-1 interacts with the immunoreceptor tyrosine-based inhibition motif on TGF-ß receptor 1 and is critical for TGF-ß signaling activation in HSCs. Functionally, Shp-1 knockout HSCs do not respond to TGF-ß-enforced HSC quiescence regulation, both in vitro and in vivo. Therefore, we identify TGF-ß-SHP-1 as a novel intrinsic regulatory mechanism for HSC quiescence maintenance.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Transdução de Sinais
/
Fator de Crescimento Transformador beta
/
Proteína Tirosina Fosfatase não Receptora Tipo 6
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China