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Title: | Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres |
Author: | Albini, Sonia Coutinho, Paula Malecova, Barbora Giordani, Lorenzo Savchenko, Alex Forcales Fernàndez, Sonia-Vanina Puri, Pier Lorenzo |
Keywords: | Epigenètica Cèl·lules mare embrionàries Cèl·lules musculars Citologia Transcripció genètica Epigenetics Embryonic stem cells Muscle cells Cytology Genetic transcription |
Issue Date: | 1-Mar-2013 |
Publisher: | Elsevier |
Abstract: | Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs) and formation of three-dimensional contractile structures for disease modeling in vitro are current challenges in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB), but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here, we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3) confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by instructing MyoD positioning and allowing chromatin remodeling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile three-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as a key epigenetic determinant of hESC commitment to the myogenic lineage and establish the molecular basis for the generation of hESC-derived myospheres exploitable for 'disease in a dish' models of muscular physiology and dysfunction. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2013.02.012 |
It is part of: | Cell Reports, 2013, vol. 3, num. 3, p. 661-670 |
URI: | http://hdl.handle.net/2445/184760 |
Related resource: | https://doi.org/10.1016/j.celrep.2013.02.012 |
ISSN: | 2211-1247 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Publicacions de projectes de recerca finançats per la UE |
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