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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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.
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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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