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 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…

• NS
  National Science Foundation

  Awards: DMS1763272, DGE-1321846, DMS1562176, 1321846
• NI
  National Institutes of Health

  Awards: AR067273, DGE-1321846, 594598, DMS1562176, R01-AR067273, R01-AR069653, AR073159, GM055246, AR069653, U01-AR073159, DMS1763272
• CI
  Canadian Institutes of Health Research
• CF
  Center for Complex Biological Systems, University of California, Irvine