mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells.
Proc Natl Acad Sci U S A
; 106(19): 7840-5, 2009 May 12.
Article
en En
| MEDLINE
| ID: mdl-19416884
Despite the recent identification of the transcriptional regulatory circuitry involving SOX2, NANOG, and OCT-4, the intracellular signaling networks that control pluripotency of human embryonic stem cells (hESCs) remain largely undefined. Here, we demonstrate an essential role for the serine/threonine protein kinase mammalian target of rapamycin (mTOR) in regulating hESC long-term undifferentiated growth. Inhibition of mTOR impairs pluripotency, prevents cell proliferation, and enhances mesoderm and endoderm activities in hESCs. At the molecular level, mTOR integrates signals from extrinsic pluripotency-supporting factors and represses the transcriptional activities of a subset of developmental and growth-inhibitory genes, as revealed by genome-wide microarray analyses. Repression of the developmental genes by mTOR is necessary for the maintenance of hESC pluripotency. These results uncover a novel signaling mechanism by which mTOR controls fate decisions in hESCs. Our findings may contribute to effective strategies for tissue repair and regeneration.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
/
Regulación de la Expresión Génica
/
Endodermo
/
Células Madre Embrionarias
/
Mesodermo
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos