CD201+ fascia progenitors choreograph injury repair

Donovan Correa-Gallegos, Haifeng Ye, Bikram Dasgupta, Aydan Sardogan, Safwen Kadri, Ravinder Kandi, Ruoxuan Dai, Yue Lin, Robert Kopplin, Disha Shantaram Shenai, Juliane Wannemacher, Ryo Ichijo, Dongsheng Jiang, Maximilian Strunz, Meshal Ansari, Illias Angelidis, Herbert B. Schiller, Thomas Volz, Hans-Günther Machens and Yuval Rinkevich ()
Additional contact information
Donovan Correa-Gallegos: Helmholtz Munich
Haifeng Ye: Helmholtz Munich
Bikram Dasgupta: Helmholtz Munich
Aydan Sardogan: Helmholtz Munich
Safwen Kadri: Helmholtz Munich
Ravinder Kandi: Helmholtz Munich
Ruoxuan Dai: Helmholtz Munich
Yue Lin: Helmholtz Munich
Robert Kopplin: Helmholtz Munich
Disha Shantaram Shenai: Helmholtz Munich
Juliane Wannemacher: Helmholtz Munich
Ryo Ichijo: Helmholtz Munich
Dongsheng Jiang: Helmholtz Munich
Maximilian Strunz: Helmholtz Munich
Meshal Ansari: Helmholtz Munich
Illias Angelidis: Helmholtz Munich
Herbert B. Schiller: Helmholtz Munich
Thomas Volz: Technical University of Munich
Hans-Günther Machens: Technical University of Munich
Yuval Rinkevich: Helmholtz Munich

Nature, 2023, vol. 623, issue 7988, 792-802

Abstract: Abstract Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation1. 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.

Date: 2023
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DOI: 10.1038/s41586-023-06725-x

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