Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases

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...

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Bibliographic Details
Published in:Nature communications Vol. 12; no. 1; pp. 3709 - 16
Main Authors: Deng, Cheng-Cheng, Hu, Yong-Fei, Zhu, Ding-Heng, Cheng, Qing, Gu, Jing-Jing, Feng, Qing-Lan, Zhang, Li-Xue, Xu, Ying-Ping, Wang, Dong, Rong, Zhili, Yang, Bin
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 17.06.2021
Nature Publishing Group
Nature Portfolio
Subjects:
13/106
13/21
13/31
13/51
14/19
38/39
38/77
45/91
631/114
631/1647/514/1949
631/61/514/1949
631/80/304
692/1807/1812
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Collagen
Collagen - genetics
Collagen - metabolism
Disease
Extracellular matrix
Extracellular Matrix - genetics
Extracellular Matrix - metabolism
Extracellular Matrix - pathology
Fibroblasts
Fibroblasts - cytology
Fibroblasts - metabolism
Fibroblasts - pathology
Fibrosis
Gene Expression Regulation - genetics
Gene Ontology
Global health
Heterogeneity
Humanities and Social Sciences
Humans
Inflammation
Keloid - genetics
Keloid - metabolism
Keloid - pathology
Ligands
Mesenchyme
Mesoderm - cytology
Mesoderm - metabolism
Mesoderm - pathology
multidisciplinary
Pathogenesis
RNA-Seq
Science
Science (multidisciplinary)
Scleroderma
Scleroderma, Systemic - genetics
Scleroderma, Systemic - metabolism
Scleroderma, Systemic - pathology
Single-Cell Analysis
Skin diseases
Skin Diseases - genetics
Skin Diseases - metabolism
Skin Diseases - pathology
Subpopulations
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. Here the authors employ scRNA-seq to explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-24110-y