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Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds
During wound healing in adult mouse skin, hair follicles and then adipocytes regenerate. Adipocytes regenerate from myofibroblasts, a specialized contractile wound fibroblast. Here we study wound fibroblast diversity using single-cell RNA-sequencing. On analysis, wound fibroblasts group into twelve...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368572/ https://www.ncbi.nlm.nih.gov/pubmed/30737373 http://dx.doi.org/10.1038/s41467-018-08247-x |
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author | Guerrero-Juarez, Christian F. Dedhia, Priya H. Jin, Suoqin Ruiz-Vega, Rolando Ma, Dennis Liu, Yuchen Yamaga, Kosuke Shestova, Olga Gay, Denise L. Yang, Zaixin Kessenbrock, Kai Nie, Qing Pear, Warren S. Cotsarelis, George Plikus, Maksim V. |
author_facet | Guerrero-Juarez, Christian F. Dedhia, Priya H. Jin, Suoqin Ruiz-Vega, Rolando Ma, Dennis Liu, Yuchen Yamaga, Kosuke Shestova, Olga Gay, Denise L. Yang, Zaixin Kessenbrock, Kai Nie, Qing Pear, Warren S. Cotsarelis, George Plikus, Maksim V. |
author_sort | Guerrero-Juarez, Christian F. |
collection | PubMed |
description | During wound healing in adult mouse skin, hair follicles and then adipocytes regenerate. Adipocytes regenerate from myofibroblasts, a specialized contractile wound fibroblast. Here we study wound fibroblast diversity using single-cell RNA-sequencing. On analysis, wound fibroblasts group into twelve clusters. Pseudotime and RNA velocity analyses reveal that some clusters likely represent consecutive differentiation states toward a contractile phenotype, while others appear to represent distinct fibroblast lineages. One subset of fibroblasts expresses hematopoietic markers, suggesting their myeloid origin. We validate this finding using single-cell western blot and single-cell RNA-sequencing on genetically labeled myofibroblasts. Using bone marrow transplantation and Cre recombinase-based lineage tracing experiments, we rule out cell fusion events and confirm that hematopoietic lineage cells give rise to a subset of myofibroblasts and rare regenerated adipocytes. In conclusion, our study reveals that wounding induces a high degree of heterogeneity among fibroblasts and recruits highly plastic myeloid cells that contribute to adipocyte regeneration. |
format | Online Article Text |
id | pubmed-6368572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63685722019-02-11 Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds Guerrero-Juarez, Christian F. Dedhia, Priya H. Jin, Suoqin Ruiz-Vega, Rolando Ma, Dennis Liu, Yuchen Yamaga, Kosuke Shestova, Olga Gay, Denise L. Yang, Zaixin Kessenbrock, Kai Nie, Qing Pear, Warren S. Cotsarelis, George Plikus, Maksim V. Nat Commun Article During wound healing in adult mouse skin, hair follicles and then adipocytes regenerate. Adipocytes regenerate from myofibroblasts, a specialized contractile wound fibroblast. Here we study wound fibroblast diversity using single-cell RNA-sequencing. On analysis, wound fibroblasts group into twelve clusters. Pseudotime and RNA velocity analyses reveal that some clusters likely represent consecutive differentiation states toward a contractile phenotype, while others appear to represent distinct fibroblast lineages. One subset of fibroblasts expresses hematopoietic markers, suggesting their myeloid origin. We validate this finding using single-cell western blot and single-cell RNA-sequencing on genetically labeled myofibroblasts. Using bone marrow transplantation and Cre recombinase-based lineage tracing experiments, we rule out cell fusion events and confirm that hematopoietic lineage cells give rise to a subset of myofibroblasts and rare regenerated adipocytes. In conclusion, our study reveals that wounding induces a high degree of heterogeneity among fibroblasts and recruits highly plastic myeloid cells that contribute to adipocyte regeneration. Nature Publishing Group UK 2019-02-08 /pmc/articles/PMC6368572/ /pubmed/30737373 http://dx.doi.org/10.1038/s41467-018-08247-x Text en © The Author(s) 2019 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 Guerrero-Juarez, Christian F. Dedhia, Priya H. Jin, Suoqin Ruiz-Vega, Rolando Ma, Dennis Liu, Yuchen Yamaga, Kosuke Shestova, Olga Gay, Denise L. Yang, Zaixin Kessenbrock, Kai Nie, Qing Pear, Warren S. Cotsarelis, George Plikus, Maksim V. Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds |
title | Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds |
title_full | Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds |
title_fullStr | Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds |
title_full_unstemmed | Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds |
title_short | Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds |
title_sort | single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368572/ https://www.ncbi.nlm.nih.gov/pubmed/30737373 http://dx.doi.org/10.1038/s41467-018-08247-x |
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