Hyperinnervation inhibits organ-level regeneration in mammalian skin - PubMed
5 hours ago
- #hyperinnervation
- #organ-level regeneration
- #wound healing
- Late embryonic full-thickness skin injuries can regenerate epithelial, mesenchymal, neuronal, and vascular tissues with proper connectivity.
- Postnatal wounds lose the ability for organ-level regeneration and exhibit hyperinnervation in the wound bed.
- A postnatal wound-specific fibroblast (PWF) population was identified through single-cell sequencing, which is absent in embryonic wounds.
- Three PWF-enriched genes (Timp1, Cxcl12, Ccl7) inhibit organ-level regeneration and cause hyperinnervation when overexpressed in embryonic wounds.
- Reducing hyperinnervation in postnatal wounds, either by depleting Cxcl12 in fibroblasts or nerve ablation, enables regeneration of diverse lineages after injury.
- The study identifies fibroblast-driven hyperinnervation as a key barrier to organ-level regeneration and demonstrates its removal can unlock regenerative potential.