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, Alba Judith, Dehesa Etxebeste, Martxel Pedro, Goicoechea Bianchi, María, Aiastui, Ana, Richaud-Patin, Yvonne, Jiménez Delgado‬, Senda, Raya, Ángel, Naldaiz Gastesi, Neia, López de Munain Arregui, Adolfo José
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/51481
Acceso en línea:http://hdl.handle.net/10810/51481
Access Level:acceso abierto
Palabra clave:CAPN3
dystrophin
induced pluripotent stem cells
LGMDR1
skeletal muscle
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spelling Patient-Specific iPSC-Derived Cellular Models of LGMDR1Mateos Aierdi, Alba JudithDehesa Etxebeste, Martxel PedroGoicoechea Bianchi, MaríaAiastui, AnaRichaud-Patin, YvonneJiménez Delgado‬, SendaRaya, ÁngelNaldaiz Gastesi, NeiaLópez de Munain Arregui, Adolfo JoséCAPN3dystrophininduced pluripotent stem cellsLGMDR1skeletal muscleLimb-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.This work has been funded by grants from Ilundain Foundation, Isabel Gemio Foundation, Fundació La Caixa, Basque Government (2015111038), Catalan Government (2017-SGR-899 and CERCA Programme), Provincial Council of Gipuzkoa (A.LdM 114/17), and Instituto de Salud Carlos III (PI14/00436, PS09/00660 and RD16/0011/0024). A.M.-A and N.N.-G. received a studentship from the Department of Education, University and Research of the Basque Government (BFI-2012-19, PRE2013-1-1168)Elsevier202120212021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/51481reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://www.sciencedirect.com/science/article/pii/S1873506121001793?via%3Dihub#!info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/3.0/es/This article is available under the Creative Commons CC-BY-NC-ND licenseAtribución-NoComercial-SinDerivadas 3.0 Españaoai:addi.ehu.eus:10810/514812026-06-18T09:23:17Z
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, Alba Judith
CAPN3
dystrophin
induced pluripotent stem cells
LGMDR1
skeletal muscle
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, Alba Judith
Dehesa Etxebeste, Martxel Pedro
Goicoechea Bianchi, María
Aiastui, Ana
Richaud-Patin, Yvonne
Jiménez Delgado‬, Senda
Raya, Ángel
Naldaiz Gastesi, Neia
López de Munain Arregui, Adolfo José
author Mateos Aierdi, Alba Judith
author_facet Mateos Aierdi, Alba Judith
Dehesa Etxebeste, Martxel Pedro
Goicoechea Bianchi, María
Aiastui, Ana
Richaud-Patin, Yvonne
Jiménez Delgado‬, Senda
Raya, Ángel
Naldaiz Gastesi, Neia
López de Munain Arregui, Adolfo José
author_role author
author2 Dehesa Etxebeste, Martxel Pedro
Goicoechea Bianchi, María
Aiastui, Ana
Richaud-Patin, Yvonne
Jiménez Delgado‬, Senda
Raya, Ángel
Naldaiz Gastesi, Neia
López de Munain Arregui, Adolfo José
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CAPN3
dystrophin
induced pluripotent stem cells
LGMDR1
skeletal muscle
topic CAPN3
dystrophin
induced pluripotent stem cells
LGMDR1
skeletal muscle
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
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/51481
url http://hdl.handle.net/10810/51481
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S1873506121001793?via%3Dihub#!
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
This article is available under the Creative Commons CC-BY-NC-ND license
Atribución-NoComercial-SinDerivadas 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/es/
This article is available under the Creative Commons CC-BY-NC-ND license
Atribución-NoComercial-SinDerivadas 3.0 España
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 reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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