Format

Send to

Choose Destination
Nat Commun. 2019 Feb 8;10(1):650. doi: 10.1038/s41467-018-08247-x.

Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds.

Author information

1
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, 92697, USA.
2
Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697, USA.
3
Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, 92697, USA.
4
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
5
Department of Mathematics, University of California, Irvine, Irvine, CA, 92697, USA.
6
Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA.
7
CEA/INSERM Inserm_U967, 92265, Fontenay-aux-Roses cedex, France.
8
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
9
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA. cotsarel@pennmedicine.upenn.edu.
10
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, 92697, USA. plikus@uci.edu.
11
Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, 92697, USA. plikus@uci.edu.
12
Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, 92697, USA. plikus@uci.edu.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center