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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
Transcripció genètica
Embryonic stem cells
Muscle cells
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:
It is part of: Cell Reports, 2013, vol. 3, num. 3, p. 661-670
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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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