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.

A regulatory loop involving Dies1 and miR-125a controls BMP4 signaling in mouse embryonic stem cells / Parisi, Silvia; Battista, Marica; Musto, Anna; Navarra, Angelica; Tarantino, Carolina; Russo, Tommaso. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 26:10(2012), pp. 3957-3968. [10.1096/fj.12-211607]

A regulatory loop involving Dies1 and miR-125a controls BMP4 signaling in mouse embryonic stem cells.

PARISI, SILVIA;BATTISTA, MARICA;MUSTO, ANNA;NAVARRA, ANGELICA;TARANTINO, CAROLINA;RUSSO, TOMMASO
2012

Abstract

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.
2012
A regulatory loop involving Dies1 and miR-125a controls BMP4 signaling in mouse embryonic stem cells / Parisi, Silvia; Battista, Marica; Musto, Anna; Navarra, Angelica; Tarantino, Carolina; Russo, Tommaso. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 26:10(2012), pp. 3957-3968. [10.1096/fj.12-211607]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/480496
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