Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres

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 myoblast...

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Detalhes bibliográficos
Autores: Albini, Sonia, Coutinho, Paula, Malecova, Barbora, Giordani, Lorenzo, Savchenko, Alex, Forcales Fernàndez, Sonia-Vanina, Puri, Pier Lorenzo
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/184760
Acesso em linha:https://hdl.handle.net/2445/184760
Access Level:acceso abierto
Palavra-chave:Epigenètica
Cèl·lules mare embrionàries
Cèl·lules musculars
Citologia
Transcripció genètica
Epigenetics
Embryonic stem cells
Muscle cells
Cytology
Genetic transcription
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spelling Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheresAlbini, SoniaCoutinho, PaulaMalecova, BarboraGiordani, LorenzoSavchenko, AlexForcales Fernàndez, Sonia-VaninaPuri, Pier LorenzoEpigenèticaCèl·lules mare embrionàriesCèl·lules muscularsCitologiaTranscripció genèticaEpigeneticsEmbryonic stem cellsMuscle cellsCytologyGenetic transcriptionDirect 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.Elsevier2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/184760Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.celrep.2013.02.012Cell Reports, 2013, vol. 3, num. 3, p. 661-670https://doi.org/10.1016/j.celrep.2013.02.012info:eu-repo/grantAgreement/EC/FP7/241440cc-by (c) Albini, Sonia et al., 2013https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1847602026-05-27T06:46:51Z
dc.title.none.fl_str_mv Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
title Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
spellingShingle Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
Albini, Sonia
Epigenètica
Cèl·lules mare embrionàries
Cèl·lules musculars
Citologia
Transcripció genètica
Epigenetics
Embryonic stem cells
Muscle cells
Cytology
Genetic transcription
title_short Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
title_full Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
title_fullStr Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
title_full_unstemmed Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
title_sort Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres
dc.creator.none.fl_str_mv Albini, Sonia
Coutinho, Paula
Malecova, Barbora
Giordani, Lorenzo
Savchenko, Alex
Forcales Fernàndez, Sonia-Vanina
Puri, Pier Lorenzo
author Albini, Sonia
author_facet Albini, Sonia
Coutinho, Paula
Malecova, Barbora
Giordani, Lorenzo
Savchenko, Alex
Forcales Fernàndez, Sonia-Vanina
Puri, Pier Lorenzo
author_role author
author2 Coutinho, Paula
Malecova, Barbora
Giordani, Lorenzo
Savchenko, Alex
Forcales Fernàndez, Sonia-Vanina
Puri, Pier Lorenzo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigenètica
Cèl·lules mare embrionàries
Cèl·lules musculars
Citologia
Transcripció genètica
Epigenetics
Embryonic stem cells
Muscle cells
Cytology
Genetic transcription
topic Epigenètica
Cèl·lules mare embrionàries
Cèl·lules musculars
Citologia
Transcripció genètica
Epigenetics
Embryonic stem cells
Muscle cells
Cytology
Genetic transcription
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/184760
url https://hdl.handle.net/2445/184760
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2013.02.012
Cell Reports, 2013, vol. 3, num. 3, p. 661-670
https://doi.org/10.1016/j.celrep.2013.02.012
info:eu-repo/grantAgreement/EC/FP7/241440
dc.rights.none.fl_str_mv cc-by (c) Albini, Sonia et al., 2013
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Albini, Sonia et al., 2013
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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