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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...

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Autores principales: Gilbert, Guillaume, Kadur Nagaraju, Chandan, Duelen, Robin, Amoni, Matthew, Bobin, Pierre, Eschenhagen, Thomas, Roderick, H. Llewelyn, Sampaolesi, Maurilio, Sipido, Karin R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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.
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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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