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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/184760
Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
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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.
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ALBINI, Sonia, COUTINHO, Paula, MALECOVA, Barbora, GIORDANI, Lorenzo, SAVCHENKO, Alex, FORCALES FERNÀNDEZ, Sonia-vanina, PURI, Pier lorenzo. Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres. _Cell Reports_. 2013. Vol. 3, núm. 3, pàgs. 661-670. [consulta: 2 de desembre de 2025]. ISSN: 2211-1247. [Disponible a: https://hdl.handle.net/2445/184760]