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miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis.
Musto, A; Navarra, A; Vocca, A; Gargiulo, A; Minopoli, G; Romano, S; Romano, M F; Russo, T; Parisi, S.
Afiliación
  • Musto A; 1] Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy [2] Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
  • Navarra A; 1] Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy [2] Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
  • Vocca A; 1] Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy [2] Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
  • Gargiulo A; 1] Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy [2] Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
  • Minopoli G; 1] Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy [2] Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
  • Romano S; Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy.
  • Romano MF; Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy.
  • Russo T; 1] Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy [2] Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
  • Parisi S; 1] Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', Via Sergio Pansini 5, Naples, Italy [2] Ceinge Biotecnologie Avanzate, Via Gaetano Salvatore 486, Naples, Italy.
Cell Death Differ ; 22(6): 1047-57, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25476774
Numerous studies have indicated that BMP4 signaling is involved in the regulation of the early steps of development. In mouse embryonic stem cells (ESCs), BMP4 is crucial to sustain pluripotency and blocks differentiation towards neural fate. Here, through a systematic analysis of miRNAs in ESCs, we establish that BMP4 signaling regulates miR-23a, 27a and 24-2, through the recruitment of phospho-Smads at the promoter of the gene encoding this miRNA cluster. Suppression of miR-23a/b, 27a/b and 24 does not affect self-renewal or pluripotency, but induces an evident change of ESC differentiation, with a significant increase of the cells undergoing apoptosis after the transition from ESCs to epiblast stem cells (EpiSCs). BMP4 has been previously reported to cause apoptosis during ESC differentiation. By blocking BMP4 signaling, we completely prevent the apoptosis induced by suppression of the miRs. This suggests that the effects of miR suppression are the result of enhanced BMP4 signaling. This hypothesis is further supported by the observation that Smad5, the transcription factor downstream of the BMP4 receptor, is targeted by the miRNAs of the 23a and 23b clusters. Altogether, our results highlight the existence of a regulatory loop, involving Smad5 and the miR-23a clusters, that modulates the apoptotic response of ESCs to BMP4.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Células Madre Embrionarias / Proteína Morfogenética Ósea 4 Límite: Animals Idioma: En Revista: Cell Death Differ Año: 2015 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Células Madre Embrionarias / Proteína Morfogenética Ósea 4 Límite: Animals Idioma: En Revista: Cell Death Differ Año: 2015 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido