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Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes
Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128860/ https://www.ncbi.nlm.nih.gov/pubmed/30194383 http://dx.doi.org/10.1038/s41467-018-05573-y |
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author | Ferguson, Gabriel B. Van Handel, Ben Bay, Maxwell Fiziev, Petko Org, Tonis Lee, Siyoung Shkhyan, Ruzanna Banks, Nicholas W. Scheinberg, Mila Wu, Ling Saitta, Biagio Elphingstone, Joseph Larson, A. Noelle Riester, Scott M. Pyle, April D. Bernthal, Nicholas M. Mikkola, Hanna KA Ernst, Jason van Wijnen, Andre J. Bonaguidi, Michael Evseenko, Denis |
author_facet | Ferguson, Gabriel B. Van Handel, Ben Bay, Maxwell Fiziev, Petko Org, Tonis Lee, Siyoung Shkhyan, Ruzanna Banks, Nicholas W. Scheinberg, Mila Wu, Ling Saitta, Biagio Elphingstone, Joseph Larson, A. Noelle Riester, Scott M. Pyle, April D. Bernthal, Nicholas M. Mikkola, Hanna KA Ernst, Jason van Wijnen, Andre J. Bonaguidi, Michael Evseenko, Denis |
author_sort | Ferguson, Gabriel B. |
collection | PubMed |
description | Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine. |
format | Online Article Text |
id | pubmed-6128860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61288602018-09-10 Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes Ferguson, Gabriel B. Van Handel, Ben Bay, Maxwell Fiziev, Petko Org, Tonis Lee, Siyoung Shkhyan, Ruzanna Banks, Nicholas W. Scheinberg, Mila Wu, Ling Saitta, Biagio Elphingstone, Joseph Larson, A. Noelle Riester, Scott M. Pyle, April D. Bernthal, Nicholas M. Mikkola, Hanna KA Ernst, Jason van Wijnen, Andre J. Bonaguidi, Michael Evseenko, Denis Nat Commun Article Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation. Network analysis delineated five tissue-specific gene modules; these modules and chromatin state analysis defined broad similarities in gene expression during cartilage specification and maturation in vitro and in vivo, including early expression and progressive silencing of muscle- and bone-specific genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem cell-derived articular chondrocytes identified that integrin alpha 4 defines 2 subsets of functionally and molecularly distinct chondrocytes characterized by their gene expression, osteochondral potential in vitro and proliferative signature in vivo. These analyses provide new insight into human musculoskeletal development and provide an essential comparative resource for disease modeling and regenerative medicine. Nature Publishing Group UK 2018-09-07 /pmc/articles/PMC6128860/ /pubmed/30194383 http://dx.doi.org/10.1038/s41467-018-05573-y Text en © The Author(s) 2018 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 Ferguson, Gabriel B. Van Handel, Ben Bay, Maxwell Fiziev, Petko Org, Tonis Lee, Siyoung Shkhyan, Ruzanna Banks, Nicholas W. Scheinberg, Mila Wu, Ling Saitta, Biagio Elphingstone, Joseph Larson, A. Noelle Riester, Scott M. Pyle, April D. Bernthal, Nicholas M. Mikkola, Hanna KA Ernst, Jason van Wijnen, Andre J. Bonaguidi, Michael Evseenko, Denis Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes |
title | Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes |
title_full | Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes |
title_fullStr | Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes |
title_full_unstemmed | Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes |
title_short | Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes |
title_sort | mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128860/ https://www.ncbi.nlm.nih.gov/pubmed/30194383 http://dx.doi.org/10.1038/s41467-018-05573-y |
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