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

CF Guerrero-Juarez, PH Dedhia, S Jin… - Nature …, 2019 - nature.com
CF Guerrero-Juarez, PH Dedhia, S Jin, R Ruiz-Vega, D Ma, Y Liu, K Yamaga, O Shestova…
Nature communications, 2019nature.com
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 …
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.
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