- 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
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.