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DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs
BACKGROUND: Cardiac disease modelling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) requires thorough insight into cardiac cell type differentiation processes. However, current methods to discriminate different cardiac cell types are mostly time-consuming, are costly an...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560887/ https://www.ncbi.nlm.nih.gov/pubmed/31186048 http://dx.doi.org/10.1186/s13148-019-0679-0 |
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author | Hoff, Kirstin Lemme, Marta Kahlert, Anne-Karin Runde, Kerstin Audain, Enrique Schuster, Dorit Scheewe, Jens Attmann, Tim Pickardt, Thomas Caliebe, Almuth Siebert, Reiner Kramer, Hans-Heiner Milting, Hendrik Hansen, Arne Ammerpohl, Ole Hitz, Marc-Phillip |
author_facet | Hoff, Kirstin Lemme, Marta Kahlert, Anne-Karin Runde, Kerstin Audain, Enrique Schuster, Dorit Scheewe, Jens Attmann, Tim Pickardt, Thomas Caliebe, Almuth Siebert, Reiner Kramer, Hans-Heiner Milting, Hendrik Hansen, Arne Ammerpohl, Ole Hitz, Marc-Phillip |
author_sort | Hoff, Kirstin |
collection | PubMed |
description | BACKGROUND: Cardiac disease modelling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) requires thorough insight into cardiac cell type differentiation processes. However, current methods to discriminate different cardiac cell types are mostly time-consuming, are costly and often provide imprecise phenotypic evaluation. DNA methylation plays a critical role during early heart development and cardiac cellular specification. We therefore investigated the DNA methylation pattern in different cardiac tissues to identify CpG loci for further cardiac cell type characterization. RESULTS: An array-based genome-wide DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChips led to the identification of 168 differentially methylated CpG loci in atrial and ventricular human heart tissue samples (n = 49) from different patients with congenital heart defects (CHD). Systematic evaluation of atrial-ventricular DNA methylation pattern in cardiac tissues in an independent sample cohort of non-failing donor hearts and cardiac patients using bisulfite pyrosequencing helped us to define a subset of 16 differentially methylated CpG loci enabling precise characterization of human atrial and ventricular cardiac tissue samples. This defined set of reproducible cardiac tissue-specific DNA methylation sites allowed us to consistently detect the cellular identity of hiPSC-CM subtypes. CONCLUSION: Testing DNA methylation of only a small set of defined CpG sites thus makes it possible to distinguish atrial and ventricular cardiac tissues and cardiac atrial and ventricular subtypes of hiPSC-CMs. This method represents a rapid and reliable system for phenotypic characterization of in vitro-generated cardiomyocytes and opens new opportunities for cardiovascular research and patient-specific therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-019-0679-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6560887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65608872019-06-14 DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs Hoff, Kirstin Lemme, Marta Kahlert, Anne-Karin Runde, Kerstin Audain, Enrique Schuster, Dorit Scheewe, Jens Attmann, Tim Pickardt, Thomas Caliebe, Almuth Siebert, Reiner Kramer, Hans-Heiner Milting, Hendrik Hansen, Arne Ammerpohl, Ole Hitz, Marc-Phillip Clin Epigenetics Research BACKGROUND: Cardiac disease modelling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) requires thorough insight into cardiac cell type differentiation processes. However, current methods to discriminate different cardiac cell types are mostly time-consuming, are costly and often provide imprecise phenotypic evaluation. DNA methylation plays a critical role during early heart development and cardiac cellular specification. We therefore investigated the DNA methylation pattern in different cardiac tissues to identify CpG loci for further cardiac cell type characterization. RESULTS: An array-based genome-wide DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChips led to the identification of 168 differentially methylated CpG loci in atrial and ventricular human heart tissue samples (n = 49) from different patients with congenital heart defects (CHD). Systematic evaluation of atrial-ventricular DNA methylation pattern in cardiac tissues in an independent sample cohort of non-failing donor hearts and cardiac patients using bisulfite pyrosequencing helped us to define a subset of 16 differentially methylated CpG loci enabling precise characterization of human atrial and ventricular cardiac tissue samples. This defined set of reproducible cardiac tissue-specific DNA methylation sites allowed us to consistently detect the cellular identity of hiPSC-CM subtypes. CONCLUSION: Testing DNA methylation of only a small set of defined CpG sites thus makes it possible to distinguish atrial and ventricular cardiac tissues and cardiac atrial and ventricular subtypes of hiPSC-CMs. This method represents a rapid and reliable system for phenotypic characterization of in vitro-generated cardiomyocytes and opens new opportunities for cardiovascular research and patient-specific therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-019-0679-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-11 /pmc/articles/PMC6560887/ /pubmed/31186048 http://dx.doi.org/10.1186/s13148-019-0679-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Hoff, Kirstin Lemme, Marta Kahlert, Anne-Karin Runde, Kerstin Audain, Enrique Schuster, Dorit Scheewe, Jens Attmann, Tim Pickardt, Thomas Caliebe, Almuth Siebert, Reiner Kramer, Hans-Heiner Milting, Hendrik Hansen, Arne Ammerpohl, Ole Hitz, Marc-Phillip DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs |
title | DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs |
title_full | DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs |
title_fullStr | DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs |
title_full_unstemmed | DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs |
title_short | DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs |
title_sort | dna methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hipsc-cms |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560887/ https://www.ncbi.nlm.nih.gov/pubmed/31186048 http://dx.doi.org/10.1186/s13148-019-0679-0 |
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