Single-cell transcriptomics reveals aberrant skin-resident cell populations and identifies fibroblasts as a determinant in rosacea

Mengting Chen, Li Yang, Peijie Zhou, Suoqin Jin, Zheng Wu, Zixin Tan, Wenqin Xiao, San Xu, Yan Zhu, Mei Wang, Dan Jian, Fangfen Liu, Yan Tang, Zhixiang Zhao, Yingxue Huang, Wei Shi, Hongfu Xie, Qing Nie (), Ben Wang (), Zhili Deng () and Ji Li ()
Additional contact information
Mengting Chen: Central South University
Li Yang: Central South University
Peijie Zhou: Peking University
Suoqin Jin: Wuhan University
Zheng Wu: Central South University
Zixin Tan: Central South University
Wenqin Xiao: Central South University
San Xu: Central South University
Yan Zhu: Central South University
Mei Wang: Central South University
Dan Jian: Central South University
Fangfen Liu: Central South University
Yan Tang: Central South University
Zhixiang Zhao: Central South University
Yingxue Huang: Central South University
Wei Shi: Central South University
Hongfu Xie: Central South University
Qing Nie: University of California Irvine
Ben Wang: Central South University
Zhili Deng: Central South University
Ji Li: Central South University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.

Date: 2024
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DOI: 10.1038/s41467-024-52946-7

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