CD201(+) fascia progenitors choreograph injury repair

Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation(1). Here we identify a multipotent fibroblast progenitor marked by CD201 expression in the fascia, the deepest connective tissue layer of the skin. Using skin injury models in mice, single-cell transcriptomics and genetic lineage tracing, ablation and gene deletion models, we demonstrate that CD201(+) progenitors control the pace of wound healing by generating multiple specialized cell types, from proinflammatory fibroblasts to myofibroblasts, in a spatiotemporally tuned sequence. We identified retinoic acid and hypoxia signalling as the entry checkpoints into proinflammatory and myofibroblast states. Modulating CD201(+) progenitor differentiation impaired the spatiotemporal appearances of fibroblasts and chronically delayed wound healing. The discovery of proinflammatory and myofibroblast progenitors and their differentiation pathways provide a new roadmap to understand and clinically treat impaired wound healing.

• Correa-Gallegos, D.
• Ye, H.
• Dasgupta, B.
• Sardogan, A.
• Kadri, S.
• Kandi, R.
• Dai, R.
• Lin, Y.
• Kopplin, R.
• Shenai, D. S.
• Wannemacher, J.
• Ichijo, R.
• Jiang, D.
• Strunz, M.
• Ansari, M.
• Angelidis, I.
• Schiller, H. B.
• Voltz, T.
• Machens, H. G.
• Rinkevich, Y.