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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599983/ https://www.ncbi.nlm.nih.gov/pubmed/34805146 http://dx.doi.org/10.3389/fcell.2021.737840 |
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author | Gilbert, Guillaume Kadur Nagaraju, Chandan Duelen, Robin Amoni, Matthew Bobin, Pierre Eschenhagen, Thomas Roderick, H. Llewelyn Sampaolesi, Maurilio Sipido, Karin R. |
author_facet | Gilbert, Guillaume Kadur Nagaraju, Chandan Duelen, Robin Amoni, Matthew Bobin, Pierre Eschenhagen, Thomas Roderick, H. Llewelyn Sampaolesi, Maurilio Sipido, Karin R. |
author_sort | Gilbert, Guillaume |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8599983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85999832021-11-19 Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Gilbert, Guillaume Kadur Nagaraju, Chandan Duelen, Robin Amoni, Matthew Bobin, Pierre Eschenhagen, Thomas Roderick, H. Llewelyn Sampaolesi, Maurilio Sipido, Karin R. Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-11-04 /pmc/articles/PMC8599983/ /pubmed/34805146 http://dx.doi.org/10.3389/fcell.2021.737840 Text en Copyright © 2021 Gilbert, Kadur Nagaraju, Duelen, Amoni, Bobin, Eschenhagen, Roderick, Sampaolesi and Sipido. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Gilbert, Guillaume Kadur Nagaraju, Chandan Duelen, Robin Amoni, Matthew Bobin, Pierre Eschenhagen, Thomas Roderick, H. Llewelyn Sampaolesi, Maurilio Sipido, Karin R. Incomplete Assembly of the Dystrophin-Associated Protein Complex in 2D and 3D-Cultured Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes |
title | 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_short | 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 |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599983/ https://www.ncbi.nlm.nih.gov/pubmed/34805146 http://dx.doi.org/10.3389/fcell.2021.737840 |
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