Single-cell RNA-seq Reveals Fibroblast Heterogeneity and Increased Mesenchymal Fibroblasts in Human Fibrotic Skin Diseases

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jun 18

PMID 34140509

Citations 146

Authors

Cheng-Cheng Deng

Yong-Fei Hu

Ding-Heng Zhu

Qing Cheng

Jing-Jing Gu

Qing-Lan Feng

Li-Xue Zhang

Ying-Ping Xu

Dong Wang

Zhili Rong

Bin Yang

Affiliations

Soon will be listed here.

Abstract

Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.

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