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1.
Nature ; 623(7988): 792-802, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37968392

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.


Subject(s)
Endothelial Protein C Receptor , Fascia , Wound Healing , Animals , Mice , Cell Differentiation , Cell Hypoxia , Cell Lineage , Disease Models, Animal , Endothelial Protein C Receptor/metabolism , Fascia/cytology , Fascia/injuries , Fascia/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism , Gene Expression Profiling , Inflammation/metabolism , Inflammation/pathology , Myofibroblasts/cytology , Myofibroblasts/metabolism , Signal Transduction , Single-Cell Gene Expression Analysis , Skin/cytology , Skin/injuries , Skin/metabolism , Tretinoin/metabolism
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