An Oct4-pRb axis, controlled by MiR-335, integrates stem cell self-renewal and cell cycle control.
Stem Cells
; 31(4): 717-28, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23307555
ABSTRACT
The pluripotency of mouse embryonic stem cells (mESCs) is controlled by a network of transcription factors, mi-RNAs, and signaling pathways. Here, we present a new regulatory circuit that connects miR-335, Oct4, and the Retinoblastoma pathway to control mESC self-renewal and differentiation. Oct4 drives the expression of Nipp1 and Ccnf that inhibit the activity of the protein phosphatase 1 (PP1) complex to establish hyperphosphorylation of the retinoblastoma protein 1 (pRb) as a hallmark feature of self-renewing mESCs. The Oct4-Nipp1/Ccnf-PP1-pRb axis promoting mESC self-renewal is under control of miR-335 that regulates Oct4 and Rb expression. During mESC differentiation, miR-335 upregulation co-operates with the transcriptional repression of Oct4 to facilitate the collapse of the Oct4-Nipp1/Ccnf-PP1-pRb axis, pRb dephosphorylation, the exit from self-renewal, and the establishment of a pRb-regulated cell cycle program. Our results introduce Oct4-dependent control of the Rb pathway as novel regulatory circuit controlling mESC self-renewal and differentiation.
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Proteína de Retinoblastoma
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MicroARNs
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Factor 3 de Transcripción de Unión a Octámeros
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Células Madre Embrionarias
Límite:
Animals
Idioma:
En
Revista:
Stem Cells
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia