Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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
_version_ 1783394008074027008
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
work_keys_str_mv AT guerrerojuarezchristianf singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT dedhiapriyah singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT jinsuoqin singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT ruizvegarolando singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT madennis singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT liuyuchen singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT yamagakosuke singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT shestovaolga singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT gaydenisel singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT yangzaixin singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT kessenbrockkai singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT nieqing singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT pearwarrens singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT cotsarelisgeorge singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds
AT plikusmaksimv singlecellanalysisrevealsfibroblastheterogeneityandmyeloidderivedadipocyteprogenitorsinmurineskinwounds