Conclusion
Our study thus advances the understanding of the roles of neural-derived cells in skin regeneration and suggests a potential therapeutic strategy for wound healing disorders.
Methods
The activity of SCs was investigated by using a cell atlas of the wound healing process, which was generated by integrating single-cell RNA sequencing (scRNA-seq) libraries covering different states of mouse back skin. The
Results
Our in silico analysis revealed the heterogeneous cellular components of skin and the dynamic interactions of neural crest derived cells (NCs) with other cell types. We found that SCs dedifferentiated at an early stage of wound repair with upregulated Wnt signaling. We also identified dedifferentiated SC (dSC) defect in diabetic wounds in both mouse and human. Wnt inhibition at the wound site repressed SC dedifferentiation, leading to defective repair. Furthermore, dSCs derived TGF-β3, which is context-dependent, promoted the migration of fibroblasts and keratinocytes. Moreover, TGF-β3 supplementation enhanced the healing of chronic wounds in diabetic mice with impaired SCs.