Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are increasingly used to study genetic diseases on a human background. However, the lack of a fully mature adult cardiomyocyte phenotype of hiPSC-CM may be limiting the scope of these studies. Muscular dystrophies and concomitant...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:b35c150cb7c84d46b27ae8cd2dd0d2492021-11-04T06:44:46ZIncomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes2296-634X10.3389/fcell.2021.737840https://doaj.org/article/b35c150cb7c84d46b27ae8cd2dd0d2492021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.737840/fullhttps://doaj.org/toc/2296-634XHuman induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are increasingly used to study genetic diseases on a human background. However, the lack of a fully mature adult cardiomyocyte phenotype of hiPSC-CM may be limiting the scope of these studies. Muscular dystrophies and concomitant cardiomyopathies result from mutations in genes encoding proteins of the dystrophin-associated protein complex (DAPC), which is a multi-protein membrane-spanning complex. We examined the expression of DAPC components in hiPSC-CM, which underwent maturation in 2D and 3D culture protocols. The results were compared with human adult cardiac tissue and isolated cardiomyocytes. We found that similarly to adult cardiomyocytes, hiPSC-CM express dystrophin, in line with previous studies on Duchenne’s disease. β-dystroglycan was also expressed, but, contrary to findings in adult cardiomyocytes, none of the sarcoglycans nor α-dystroglycan were, despite the presence of their mRNA. In conclusion, despite the robust expression of dystrophin, the absence of several other DAPC protein components cautions for reliance on commonly used protocols for hiPSC-CM maturation for functional assessment of the complete DAPC.Guillaume GilbertChandan Kadur NagarajuRobin DuelenMatthew AmoniPierre BobinPierre BobinThomas EschenhagenThomas EschenhagenH. Llewelyn RoderickMaurilio SampaolesiKarin R. SipidoFrontiers Media S.A.articledystrophin-associated glycoprotein complexhuman induced pluripotent stem cellshiPSC-derived cardiomyocytessarcoglycanopathyhiPSC cardiomyocyte maturationDuchenne muscular dystrophyBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021) |
institution |
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DOAJ |
language |
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topic |
dystrophin-associated glycoprotein complex human induced pluripotent stem cells hiPSC-derived cardiomyocytes sarcoglycanopathy hiPSC cardiomyocyte maturation Duchenne muscular dystrophy Biology (General) QH301-705.5 |
spellingShingle |
dystrophin-associated glycoprotein complex human induced pluripotent stem cells hiPSC-derived cardiomyocytes sarcoglycanopathy hiPSC cardiomyocyte maturation Duchenne muscular dystrophy Biology (General) QH301-705.5 Guillaume Gilbert Chandan Kadur Nagaraju Robin Duelen Matthew Amoni Pierre Bobin Pierre Bobin Thomas Eschenhagen Thomas Eschenhagen H. Llewelyn Roderick Maurilio Sampaolesi Karin R. Sipido Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes |
description |
Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are increasingly used to study genetic diseases on a human background. However, the lack of a fully mature adult cardiomyocyte phenotype of hiPSC-CM may be limiting the scope of these studies. Muscular dystrophies and concomitant cardiomyopathies result from mutations in genes encoding proteins of the dystrophin-associated protein complex (DAPC), which is a multi-protein membrane-spanning complex. We examined the expression of DAPC components in hiPSC-CM, which underwent maturation in 2D and 3D culture protocols. The results were compared with human adult cardiac tissue and isolated cardiomyocytes. We found that similarly to adult cardiomyocytes, hiPSC-CM express dystrophin, in line with previous studies on Duchenne’s disease. β-dystroglycan was also expressed, but, contrary to findings in adult cardiomyocytes, none of the sarcoglycans nor α-dystroglycan were, despite the presence of their mRNA. In conclusion, despite the robust expression of dystrophin, the absence of several other DAPC protein components cautions for reliance on commonly used protocols for hiPSC-CM maturation for functional assessment of the complete DAPC. |
format |
article |
author |
Guillaume Gilbert Chandan Kadur Nagaraju Robin Duelen Matthew Amoni Pierre Bobin Pierre Bobin Thomas Eschenhagen Thomas Eschenhagen H. Llewelyn Roderick Maurilio Sampaolesi Karin R. Sipido |
author_facet |
Guillaume Gilbert Chandan Kadur Nagaraju Robin Duelen Matthew Amoni Pierre Bobin Pierre Bobin Thomas Eschenhagen Thomas Eschenhagen H. Llewelyn Roderick Maurilio Sampaolesi Karin R. Sipido |
author_sort |
Guillaume Gilbert |
title |
Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes |
title_short |
Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes |
title_full |
Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes |
title_fullStr |
Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes |
title_full_unstemmed |
Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes |
title_sort |
incomplete assembly of the dystrophin-associated protein complex in 2d and 3d-cultured human induced pluripotent stem cell-derived cardiomyocytes |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/b35c150cb7c84d46b27ae8cd2dd0d249 |
work_keys_str_mv |
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