Single-Cell Analysis Reveals Fibroblast Heterogeneity and Myeloid-Derived Adipocyte Progenitors in Murine Skin Wounds

The study used single-cell RNA sequencing to explore the diversity of fibroblasts in murine skin wounds, identifying 12 distinct fibroblast clusters and revealing significant heterogeneity. It was found that fibroblasts differentiate into myofibroblasts, which are key for fat regeneration, and that myeloid cells can convert into fibroblasts and potentially into myofibroblasts during wound repair. Bone marrow transplantation experiments confirmed that hematopoietic lineage cells can differentiate into myofibroblasts and adipocytes in the wound dermis. The study included a total of 116 genetically marked contractile cells isolated from day 12 wounds for scRNA-seq, and in bone marrow transplantation mice, about 30% of cells at 28 days post-wounding and 2 months post-wounding were from the hematopoietic lineage. Additionally, the study found that hematopoietic lineage cells can contribute to fat cell populations in wound healing, with occasional lacZ-positive de novo adipocytes observed in the hair-bearing wounds of Retn-lacZ HSCs BMT mice (n=72 animals). The findings suggest that hematopoietic cells can directly convert to adipocytes without cell fusion and that myeloid progenitors mediate this process during wound healing.