Rare Gli1+ perivascular fibroblasts promote skin wound repair

ABSTRACT Growing evidence suggests that perivascular cells play important roles in tissue repair of various organs. In the skin, the contribution and importance of these cells for wound repair is not resolved. Here we demonstrate that a specific Gli1+ subpopulation residing in the perivascular niche serves as an important cellular source for wound healing fibroblast. First, we show that Gli1 expression marks small subsets of both pericytes and perivascular adventitial cells. Upon injury both cell types rapidly responded already within their original niche, however only the progeny of Gli1+ adventitial cells expanded and differentiated into wound-contracting myofibroblasts. Genetic ablation of these cells significantly impaired wound healing, which was associated with the reduction of aSMA+ myofibroblast-mediated wound contraction. After wound closure these cells reverted to an aSMA-negative fibroblast state, and intriguingly, they persisted in wounds over long term and adopted a non-fibrotic fibroblast signature. In sum, our data sheds new light on the functional diversity of perivascular-cell subtypes in the skin, and proposes a new mesenchymal cell source that promotes wound healing.