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Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function
Tight control of cell fate choices is crucial for normal development. Here we show that lamin A/C plays a key role in chromatin organization in embryonic stem cells (ESCs), which safeguards naïve pluripotency and ensures proper cell fate choices during cardiogenesis. We report changes in chromatin c...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636150/ https://www.ncbi.nlm.nih.gov/pubmed/36333314 http://dx.doi.org/10.1038/s41467-022-34366-7 |
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author | Wang, Yinuo Elsherbiny, Adel Kessler, Linda Cordero, Julio Shi, Haojie Serke, Heike Lityagina, Olga Trogisch, Felix A. Mohammadi, Mona Malek El-Battrawy, Ibrahim Backs, Johannes Wieland, Thomas Heineke, Joerg Dobreva, Gergana |
author_facet | Wang, Yinuo Elsherbiny, Adel Kessler, Linda Cordero, Julio Shi, Haojie Serke, Heike Lityagina, Olga Trogisch, Felix A. Mohammadi, Mona Malek El-Battrawy, Ibrahim Backs, Johannes Wieland, Thomas Heineke, Joerg Dobreva, Gergana |
author_sort | Wang, Yinuo |
collection | PubMed |
description | Tight control of cell fate choices is crucial for normal development. Here we show that lamin A/C plays a key role in chromatin organization in embryonic stem cells (ESCs), which safeguards naïve pluripotency and ensures proper cell fate choices during cardiogenesis. We report changes in chromatin compaction and localization of cardiac genes in Lmna−/− ESCs resulting in precocious activation of a transcriptional program promoting cardiomyocyte versus endothelial cell fate. This is accompanied by premature cardiomyocyte differentiation, cell cycle withdrawal and abnormal contractility. Gata4 is activated by lamin A/C loss and Gata4 silencing or haploinsufficiency rescues the aberrant cardiovascular cell fate choices induced by lamin A/C deficiency. We uncover divergent functions of lamin A/C in naïve pluripotent stem cells and cardiomyocytes, which have distinct contributions to the transcriptional alterations of patients with LMNA-associated cardiomyopathy. We conclude that disruption of lamin A/C-dependent chromatin architecture in ESCs is a primary event in LMNA loss-of-function cardiomyopathy. |
format | Online Article Text |
id | pubmed-9636150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96361502022-11-06 Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function Wang, Yinuo Elsherbiny, Adel Kessler, Linda Cordero, Julio Shi, Haojie Serke, Heike Lityagina, Olga Trogisch, Felix A. Mohammadi, Mona Malek El-Battrawy, Ibrahim Backs, Johannes Wieland, Thomas Heineke, Joerg Dobreva, Gergana Nat Commun Article Tight control of cell fate choices is crucial for normal development. Here we show that lamin A/C plays a key role in chromatin organization in embryonic stem cells (ESCs), which safeguards naïve pluripotency and ensures proper cell fate choices during cardiogenesis. We report changes in chromatin compaction and localization of cardiac genes in Lmna−/− ESCs resulting in precocious activation of a transcriptional program promoting cardiomyocyte versus endothelial cell fate. This is accompanied by premature cardiomyocyte differentiation, cell cycle withdrawal and abnormal contractility. Gata4 is activated by lamin A/C loss and Gata4 silencing or haploinsufficiency rescues the aberrant cardiovascular cell fate choices induced by lamin A/C deficiency. We uncover divergent functions of lamin A/C in naïve pluripotent stem cells and cardiomyocytes, which have distinct contributions to the transcriptional alterations of patients with LMNA-associated cardiomyopathy. We conclude that disruption of lamin A/C-dependent chromatin architecture in ESCs is a primary event in LMNA loss-of-function cardiomyopathy. Nature Publishing Group UK 2022-11-04 /pmc/articles/PMC9636150/ /pubmed/36333314 http://dx.doi.org/10.1038/s41467-022-34366-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Yinuo Elsherbiny, Adel Kessler, Linda Cordero, Julio Shi, Haojie Serke, Heike Lityagina, Olga Trogisch, Felix A. Mohammadi, Mona Malek El-Battrawy, Ibrahim Backs, Johannes Wieland, Thomas Heineke, Joerg Dobreva, Gergana Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function |
title | Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function |
title_full | Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function |
title_fullStr | Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function |
title_full_unstemmed | Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function |
title_short | Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function |
title_sort | lamin a/c-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636150/ https://www.ncbi.nlm.nih.gov/pubmed/36333314 http://dx.doi.org/10.1038/s41467-022-34366-7 |
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