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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Vydané v:	Nature communications Ročník 12; číslo 1; s. 3709 - 16
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 17.06.2021 Nature Publishing Group Nature Portfolio
Predmet:	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
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-021-24110-y