Albini, SoniaCoutinho, PaulaMalecova, BarboraGiordani, LorenzoSavchenko, AlexForcales Fernàndez, Sonia-VaninaPuri, Pier Lorenzo2022-04-052022-04-052013-03-012211-1247https://hdl.handle.net/2445/184760Direct 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.10 p.application/pdfengcc-by (c) Albini, Sonia et al., 2013https://creativecommons.org/licenses/by/4.0/EpigenèticaCèl·lules mare embrionàriesCèl·lules muscularsCitologiaTranscripció genèticaEpigeneticsEmbryonic stem cellsMuscle cellsCytologyGenetic transcriptioninfo:eu-repo/semantics/article6848862022-04-05info:eu-repo/semantics/openAccess23478022