Integrative spatial transcriptomic and chromatin-resolved analysis defines fascia-inclusive fibroblast niche organization in human surgical wound repair

We integrated fascia-inclusive spatial transcriptomic profiles with single-cell transcriptomic and chromatin-accessibility reference maps to construct fibroblast-centered multimodal spatial graphs of human surgical wounds. This analysis generated a human fascia-resolved atlas of wound repair in which fibroblasts formed recurrent niche architectures spanning fascia-to-dermis trajectories aligned with regenerative and fibrotic wound states. Cross-dataset graph analysis prioritized niche circuits associated with retinoid metabolism, mechanotransduction, and stromal–immune coupling, with support from independent cohorts and complementary analyses. The resulting framework nominated candidate regulators linked to fibroblast-state transitions, matrix remodeling, and fibrotic progression.