CD81 is essential for the re-entry of hematopoietic stem cells to quiescence following stress-induced proliferation via deactivation of the Akt pathway.
PLoS Biol
; 9(9): e1001148, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21931533
ABSTRACT
The regulatory mechanisms governing the cell cycle progression of hematopoietic stem cells (HSCs) are well characterized, but those responsible for the return of proliferating HSCs to a quiescent state remain largely unknown. Here, we present evidence that CD81, a tetraspanin molecule acutely responsive to proliferative stress, is essential for the maintenance of long-term repopulating HSCs. Cd81(-/-) HSCs showed a marked engraftment defect when transplanted into secondary recipient mice and a significantly delayed return to quiescence when stimulated to proliferate with 5-fluorouracil (5FU). In addition, we found that CD81 proteins form a polarized patch when HSCs are returning to quiescence. Thus, we propose that the spatial distribution of CD81 during the HSC recovery phase drives proliferative HSC to quiescence, and is important to preserve the self-renewal properties. Here, we show that lack of CD81 leads to loss of HSC self-renewal, and the clustering of CD81 on HSC membrane results in deactivation of Akt, which subsequently leads to nuclear translocation of FoxO1a. Thus, CD81 functions as part of a previously undefined mechanism that prohibits excessive proliferation of HSCs exposed to environmental stress.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Sistema de Sinalização das MAP Quinases
/
Proliferação de Células
/
Proteínas Proto-Oncogênicas c-akt
/
Tetraspanina 28
Limite:
Animals
Idioma:
En
Revista:
PLoS Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos