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Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture
Human induced pluripotent stem cells (hiPSCs) represent an almost limitless source of cells for disease modelling and drug screening applications. Here we established an efficient and robust 3D platform for cardiomyocyte (CMs) production from hiPSCs, solely through small-molecule-based temporal modu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592905/ https://www.ncbi.nlm.nih.gov/pubmed/31239450 http://dx.doi.org/10.1038/s41598-019-45047-9 |
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author | Branco, Mariana A. Cotovio, João P. Rodrigues, Carlos A. V. Vaz, Sandra H. Fernandes, Tiago G. Moreira, Leonilde M. Cabral, Joaquim M. S. Diogo, Maria Margarida |
author_facet | Branco, Mariana A. Cotovio, João P. Rodrigues, Carlos A. V. Vaz, Sandra H. Fernandes, Tiago G. Moreira, Leonilde M. Cabral, Joaquim M. S. Diogo, Maria Margarida |
author_sort | Branco, Mariana A. |
collection | PubMed |
description | Human induced pluripotent stem cells (hiPSCs) represent an almost limitless source of cells for disease modelling and drug screening applications. Here we established an efficient and robust 3D platform for cardiomyocyte (CMs) production from hiPSCs, solely through small-molecule-based temporal modulation of the Wnt signalling, which generates more than 90% cTNT(+) cells. The impact of performing the differentiation process in 3D conditions as compared to a 2D culture system, was characterized by transcriptomic analysis by using data collected from sequential stages of 2D and 3D culture. We highlight that performing an initial period of hiPSC aggregation before cardiac differentiation primed hiPSCs towards an earlier mesendoderm lineage differentiation, via TGF-β/Nodal signaling stabilization. Importantly, it was also found that CMs in the 3D microenvironment mature earlier and show an improved communication system, which we suggested to be responsible for a higher structural and functional maturation of 3D cardiac aggregates. |
format | Online Article Text |
id | pubmed-6592905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65929052019-07-03 Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture Branco, Mariana A. Cotovio, João P. Rodrigues, Carlos A. V. Vaz, Sandra H. Fernandes, Tiago G. Moreira, Leonilde M. Cabral, Joaquim M. S. Diogo, Maria Margarida Sci Rep Article Human induced pluripotent stem cells (hiPSCs) represent an almost limitless source of cells for disease modelling and drug screening applications. Here we established an efficient and robust 3D platform for cardiomyocyte (CMs) production from hiPSCs, solely through small-molecule-based temporal modulation of the Wnt signalling, which generates more than 90% cTNT(+) cells. The impact of performing the differentiation process in 3D conditions as compared to a 2D culture system, was characterized by transcriptomic analysis by using data collected from sequential stages of 2D and 3D culture. We highlight that performing an initial period of hiPSC aggregation before cardiac differentiation primed hiPSCs towards an earlier mesendoderm lineage differentiation, via TGF-β/Nodal signaling stabilization. Importantly, it was also found that CMs in the 3D microenvironment mature earlier and show an improved communication system, which we suggested to be responsible for a higher structural and functional maturation of 3D cardiac aggregates. Nature Publishing Group UK 2019-06-25 /pmc/articles/PMC6592905/ /pubmed/31239450 http://dx.doi.org/10.1038/s41598-019-45047-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Branco, Mariana A. Cotovio, João P. Rodrigues, Carlos A. V. Vaz, Sandra H. Fernandes, Tiago G. Moreira, Leonilde M. Cabral, Joaquim M. S. Diogo, Maria Margarida Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture |
title | Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture |
title_full | Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture |
title_fullStr | Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture |
title_full_unstemmed | Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture |
title_short | Transcriptomic analysis of 3D Cardiac Differentiation of Human Induced Pluripotent Stem Cells Reveals Faster Cardiomyocyte Maturation Compared to 2D Culture |
title_sort | transcriptomic analysis of 3d cardiac differentiation of human induced pluripotent stem cells reveals faster cardiomyocyte maturation compared to 2d culture |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592905/ https://www.ncbi.nlm.nih.gov/pubmed/31239450 http://dx.doi.org/10.1038/s41598-019-45047-9 |
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