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Myc-dependent dedifferentiation of Gata6(+) epidermal cells resembles reversal of terminal differentiation
Dedifferentiation is the process by which terminally differentiated cells acquire the properties of stem cells. During mouse skin wound healing, the differentiated Gata6-lineage positive cells of the sebaceous duct are able to dedifferentiate. Here we have integrated lineage tracing and single-cell...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10567550/ https://www.ncbi.nlm.nih.gov/pubmed/37735598 http://dx.doi.org/10.1038/s41556-023-01234-5 |
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author | Bernabé-Rubio, Miguel Ali, Shahnawaz Bhosale, Priyanka G. Goss, Georgina Mobasseri, Seyedeh Atefeh Tapia-Rojo, Rafael Zhu, Tong Hiratsuka, Toru Battilocchi, Matteo Tomás, Inês M. Ganier, Clarisse Garcia-Manyes, Sergi Watt, Fiona M. |
author_facet | Bernabé-Rubio, Miguel Ali, Shahnawaz Bhosale, Priyanka G. Goss, Georgina Mobasseri, Seyedeh Atefeh Tapia-Rojo, Rafael Zhu, Tong Hiratsuka, Toru Battilocchi, Matteo Tomás, Inês M. Ganier, Clarisse Garcia-Manyes, Sergi Watt, Fiona M. |
author_sort | Bernabé-Rubio, Miguel |
collection | PubMed |
description | Dedifferentiation is the process by which terminally differentiated cells acquire the properties of stem cells. During mouse skin wound healing, the differentiated Gata6-lineage positive cells of the sebaceous duct are able to dedifferentiate. Here we have integrated lineage tracing and single-cell mRNA sequencing to uncover the underlying mechanism. Gata6-lineage positive and negative epidermal stem cells in wounds are transcriptionally indistinguishable. Furthermore, in contrast to reprogramming of induced pluripotent stem cells, the same genes are expressed in the epidermal dedifferentiation and differentiation trajectories, indicating that dedifferentiation does not involve adoption of a new cell state. We demonstrate that dedifferentiation is not only induced by wounding, but also by retinoic acid treatment or mechanical expansion of the epidermis. In all three cases, dedifferentiation is dependent on the master transcription factor c-Myc. Mechanotransduction and actin-cytoskeleton remodelling are key features of dedifferentiation. Our study elucidates the molecular basis of epidermal dedifferentiation, which may be generally applicable to adult tissues. |
format | Online Article Text |
id | pubmed-10567550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105675502023-10-13 Myc-dependent dedifferentiation of Gata6(+) epidermal cells resembles reversal of terminal differentiation Bernabé-Rubio, Miguel Ali, Shahnawaz Bhosale, Priyanka G. Goss, Georgina Mobasseri, Seyedeh Atefeh Tapia-Rojo, Rafael Zhu, Tong Hiratsuka, Toru Battilocchi, Matteo Tomás, Inês M. Ganier, Clarisse Garcia-Manyes, Sergi Watt, Fiona M. Nat Cell Biol Article Dedifferentiation is the process by which terminally differentiated cells acquire the properties of stem cells. During mouse skin wound healing, the differentiated Gata6-lineage positive cells of the sebaceous duct are able to dedifferentiate. Here we have integrated lineage tracing and single-cell mRNA sequencing to uncover the underlying mechanism. Gata6-lineage positive and negative epidermal stem cells in wounds are transcriptionally indistinguishable. Furthermore, in contrast to reprogramming of induced pluripotent stem cells, the same genes are expressed in the epidermal dedifferentiation and differentiation trajectories, indicating that dedifferentiation does not involve adoption of a new cell state. We demonstrate that dedifferentiation is not only induced by wounding, but also by retinoic acid treatment or mechanical expansion of the epidermis. In all three cases, dedifferentiation is dependent on the master transcription factor c-Myc. Mechanotransduction and actin-cytoskeleton remodelling are key features of dedifferentiation. Our study elucidates the molecular basis of epidermal dedifferentiation, which may be generally applicable to adult tissues. Nature Publishing Group UK 2023-09-21 2023 /pmc/articles/PMC10567550/ /pubmed/37735598 http://dx.doi.org/10.1038/s41556-023-01234-5 Text en © The Author(s) 2023 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 Bernabé-Rubio, Miguel Ali, Shahnawaz Bhosale, Priyanka G. Goss, Georgina Mobasseri, Seyedeh Atefeh Tapia-Rojo, Rafael Zhu, Tong Hiratsuka, Toru Battilocchi, Matteo Tomás, Inês M. Ganier, Clarisse Garcia-Manyes, Sergi Watt, Fiona M. Myc-dependent dedifferentiation of Gata6(+) epidermal cells resembles reversal of terminal differentiation |
title | Myc-dependent dedifferentiation of Gata6(+) epidermal cells resembles reversal of terminal differentiation |
title_full | Myc-dependent dedifferentiation of Gata6(+) epidermal cells resembles reversal of terminal differentiation |
title_fullStr | Myc-dependent dedifferentiation of Gata6(+) epidermal cells resembles reversal of terminal differentiation |
title_full_unstemmed | Myc-dependent dedifferentiation of Gata6(+) epidermal cells resembles reversal of terminal differentiation |
title_short | Myc-dependent dedifferentiation of Gata6(+) epidermal cells resembles reversal of terminal differentiation |
title_sort | myc-dependent dedifferentiation of gata6(+) epidermal cells resembles reversal of terminal differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10567550/ https://www.ncbi.nlm.nih.gov/pubmed/37735598 http://dx.doi.org/10.1038/s41556-023-01234-5 |
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