期刊
FASEB JOURNAL
卷 26, 期 10, 页码 3957-3968出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.12-211607
关键词
differentiation; miRNA gene regulation; signal transduction; transforming growth factor-beta; bone morphogenetic protein 4
资金
- EC-Sirocco Consortium
- Associazione Italiana Ricerca sul Cancro
- Italian Ministry of Research [PON 01_02782]
Bone morphogenetic protein 4 (BMP4) plays an important role in maintaining embryonic stem cells (ESCs) in the undifferentiated state and in the regulation of lineage commitment. We recently identified a transmembrane protein, named Dies1, the suppression of which by RNA interference blocks mouse ESC differentiation by interfering with the BMP4 signaling. We asked whether modulation of Dies1 levels could be a physiological mechanism to regulate ESC pluripotency and/or differentiation. We demonstrated that miR-125a targets Dies1 and regulates its expression in ESCs. The overexpression of miR-125a impairs differentiation, and this effect is specifically mediated by Dies1 down-regulation and accompanied by a decrease of BMP4 signaling. We also found that Dies1 is associated with BMP4 receptor complex and that BMP4 activates the transcription of miR-125a gene. Therefore, a feedback loop exists that sets ESC sensitivity to BMP4. The analysis of this regulatory mechanism revealed that miR-125a overexpression and the consequent inhibition of the BMP4 signaling arrest the cells in the epiblast stem cell (epiSC) status, due to the concomitant activation of the Nodal/Activin pathway.-Parisi, S., Battista, M., Musto, A., Navarra, A., Tarantino, C., Russo, T. A regulatory loop involving Dies1 and miR-125a controls BMP4 signaling in mouse embryonic stem cells. FASEB J. 26, 3957-3968 (2012). www.fasebj.org
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