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.
Highlights
During wound healing in adult mouse skin, hair follicles and adipocytes regenerate
Cluster C8 cells were identified as B lymphocytes (~3%) and C12 as dendritic cells (~1%)
Cluster C5 cells were enriched for endothelial markers Cav[1], Cd34, Cd93, Ly6e, Ly6c1, and Pecam[1], while cluster C13 cells—for lymphatic endothelial markers Ccl21a, Lyve[1], Pdpn, and Prox[1]
Summary
During wound healing in adult mouse skin, hair follicles and adipocytes regenerate. While small wounds,
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