Patient-specific iPSC-derived cellular models of LGMDR1

Limb-girdle muscular dystrophy recessive 1 (LGMDR1) represents one of the most common types of LGMD in the population, where patients develop a progressive muscle degeneration. The disease is caused by mutations in calpain 3 gene, with over 500 mutations reported to date. However, the molecular even...

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Autores: Mateos Aierdi, A.J., Dehesa Etxebeste, M., Goicoechea, M., Aiastui, A., Richaud-Patin, Yvonne, Jiménez-Delgado, Senda, Raya Chamorro, Ángel, Naldaiz Gastesi, N., López de Munain, Adolfo
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/178781
Acceso en línea:https://hdl.handle.net/2445/178781
Access Level:acceso abierto
Palabra clave:Distròfia muscular
Cèl·lules mare
Muscular dystrophy
Stem cells
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spelling Patient-specific iPSC-derived cellular models of LGMDR1Mateos Aierdi, A.J.Dehesa Etxebeste, M.Goicoechea, M.Aiastui, A.Richaud-Patin, YvonneJiménez-Delgado, SendaRaya Chamorro, ÁngelNaldaiz Gastesi, N.López de Munain, AdolfoDistròfia muscularCèl·lules mareMuscular dystrophyStem cellsLimb-girdle muscular dystrophy recessive 1 (LGMDR1) represents one of the most common types of LGMD in the population, where patients develop a progressive muscle degeneration. The disease is caused by mutations in calpain 3 gene, with over 500 mutations reported to date. However, the molecular events that lead to muscle wasting are not clear, nor the reasons for the great clinical variability among patients, and this has so far hindered the development of effective therapies. Here we generate human induced pluripotent stem cells (iPSCs) from skin fibroblasts of 2 healthy controls and 4 LGMDR1 patients with different mutations. The generated lines were able to differentiate into myogenic progenitors and myotubes in vitro and in vivo, upon a transient PAX7 overexpressing protocol. Thus, we have generated myogenic cellular models of LGMDR1 that harbor different CAPN3 mutations within a human genetic background, and which do not derive from muscular biopsies. These models will allow us to investigate disease mechanisms and test therapies. Despite the variability found among iPSC lines that was unrelated to CAPN3 mutations, we found that patient-derived myogenic progenitors and myotubes express lower levels of DMD, which codes a key protein in satellite cell regulation and myotube maturation.Elsevier BV2021info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2445/178781Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.scr.2021.102333Stem Cell Research, 2021, vol. 53, p. 102333https://doi.org/10.1016/j.scr.2021.102333cc by-nc-nd (c) Mateos Aierdi, A.J. et al., 2021http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1787812026-05-27T06:46:51Z
dc.title.none.fl_str_mv Patient-specific iPSC-derived cellular models of LGMDR1
title Patient-specific iPSC-derived cellular models of LGMDR1
spellingShingle Patient-specific iPSC-derived cellular models of LGMDR1
Mateos Aierdi, A.J.
Distròfia muscular
Cèl·lules mare
Muscular dystrophy
Stem cells
title_short Patient-specific iPSC-derived cellular models of LGMDR1
title_full Patient-specific iPSC-derived cellular models of LGMDR1
title_fullStr Patient-specific iPSC-derived cellular models of LGMDR1
title_full_unstemmed Patient-specific iPSC-derived cellular models of LGMDR1
title_sort Patient-specific iPSC-derived cellular models of LGMDR1
dc.creator.none.fl_str_mv Mateos Aierdi, A.J.
Dehesa Etxebeste, M.
Goicoechea, M.
Aiastui, A.
Richaud-Patin, Yvonne
Jiménez-Delgado, Senda
Raya Chamorro, Ángel
Naldaiz Gastesi, N.
López de Munain, Adolfo
author Mateos Aierdi, A.J.
author_facet Mateos Aierdi, A.J.
Dehesa Etxebeste, M.
Goicoechea, M.
Aiastui, A.
Richaud-Patin, Yvonne
Jiménez-Delgado, Senda
Raya Chamorro, Ángel
Naldaiz Gastesi, N.
López de Munain, Adolfo
author_role author
author2 Dehesa Etxebeste, M.
Goicoechea, M.
Aiastui, A.
Richaud-Patin, Yvonne
Jiménez-Delgado, Senda
Raya Chamorro, Ángel
Naldaiz Gastesi, N.
López de Munain, Adolfo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Distròfia muscular
Cèl·lules mare
Muscular dystrophy
Stem cells
topic Distròfia muscular
Cèl·lules mare
Muscular dystrophy
Stem cells
description Limb-girdle muscular dystrophy recessive 1 (LGMDR1) represents one of the most common types of LGMD in the population, where patients develop a progressive muscle degeneration. The disease is caused by mutations in calpain 3 gene, with over 500 mutations reported to date. However, the molecular events that lead to muscle wasting are not clear, nor the reasons for the great clinical variability among patients, and this has so far hindered the development of effective therapies. Here we generate human induced pluripotent stem cells (iPSCs) from skin fibroblasts of 2 healthy controls and 4 LGMDR1 patients with different mutations. The generated lines were able to differentiate into myogenic progenitors and myotubes in vitro and in vivo, upon a transient PAX7 overexpressing protocol. Thus, we have generated myogenic cellular models of LGMDR1 that harbor different CAPN3 mutations within a human genetic background, and which do not derive from muscular biopsies. These models will allow us to investigate disease mechanisms and test therapies. Despite the variability found among iPSC lines that was unrelated to CAPN3 mutations, we found that patient-derived myogenic progenitors and myotubes express lower levels of DMD, which codes a key protein in satellite cell regulation and myotube maturation.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/178781
url https://hdl.handle.net/2445/178781
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.scr.2021.102333
Stem Cell Research, 2021, vol. 53, p. 102333
https://doi.org/10.1016/j.scr.2021.102333
dc.rights.none.fl_str_mv cc by-nc-nd (c) Mateos Aierdi, A.J. et al., 2021
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Mateos Aierdi, A.J. et al., 2021
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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 15.301629

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