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

Author

Listed:
  • Cheng-Cheng Deng

    (Dermatology Hospital, Southern Medical University)

  • Yong-Fei Hu

    (Dermatology Hospital, Southern Medical University
    School of Basic Medical Sciences, Southern Medical University)

  • Ding-Heng Zhu

    (Dermatology Hospital, Southern Medical University)

  • Qing Cheng

    (Dermatology Hospital, Southern Medical University)

  • Jing-Jing Gu

    (Dermatology Hospital, Southern Medical University)

  • Qing-Lan Feng

    (Dermatology Hospital, Southern Medical University)

  • Li-Xue Zhang

    (Dermatology Hospital, Southern Medical University)

  • Ying-Ping Xu

    (Dermatology Hospital, Southern Medical University)

  • Dong Wang

    (Dermatology Hospital, Southern Medical University
    School of Basic Medical Sciences, Southern Medical University)

  • Zhili Rong

    (Dermatology Hospital, Southern Medical University
    Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University
    State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Key Laboratory of Organ Failure Research (Ministry of Education))

  • Bin Yang

    (Dermatology Hospital, Southern Medical University)

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.

Suggested Citation

  • 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, 2021. "Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24110-y
    DOI: 10.1038/s41467-021-24110-y
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    1. Xiaojie Cai & Maoying Han & Fangzhou Lou & Yang Sun & Qianqian Yin & Libo Sun & Zhikai Wang & Xiangxiao Li & Hong Zhou & Zhenyao Xu & Hong Wang & Siyu Deng & Xichen Zheng & Taiyu Zhang & Qun Li & Bin , 2023. "Tenascin C+ papillary fibroblasts facilitate neuro-immune interaction in a mouse model of psoriasis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Meiling Zheng & Zhi Hu & Xiaole Mei & Lianlian Ouyang & Yang Song & Wenhui Zhou & Yi Kong & Ruifang Wu & Shijia Rao & Hai Long & Wei Shi & Hui Jing & Shuang Lu & Haijing Wu & Sujie Jia & Qianjin Lu & , 2022. "Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Sabrina Schütz & Llorenç Solé-Boldo & Carlota Lucena-Porcel & Jochen Hoffmann & Alexander Brobeil & Anke S. Lonsdorf & Manuel Rodríguez-Paredes & Frank Lyko, 2023. "Functionally distinct cancer-associated fibroblast subpopulations establish a tumor promoting environment in squamous cell carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. LiangYu Zhao & Sha Han & HengChuan Su & JianYing Li & ErLei Zhi & Peng Li & ChenCheng Yao & RuHui Tian & HuiXing Chen & HuiRong Chen & JiaQiang Luo & ChenKun Shi & ZhiYong Ji & JianLin Hu & Gang Wu & , 2022. "Single-cell transcriptome atlas of the human corpus cavernosum," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Christine Bangert & Natalia Alkon & Sumanth Chennareddy & Tamara Arnoldner & Jasmine P. Levine & Magdalena Pilz & Marco A. Medjimorec & John Ruggiero & Emry R. Cohenour & Constanze Jonak & William Dam, 2024. "Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Durba Pal & Subhadip Ghatak & Kanhaiya Singh & Ahmed Safwat Abouhashem & Manishekhar Kumar & Mohamed S El Masry & Sujit K. Mohanty & Ravichand Palakurti & Yashika Rustagi & Saba Tabasum & Dolly K. Kho, 2023. "Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Paula Punzon-Jimenez & Alba Machado-Lopez & Raul Perez-Moraga & Jaime Llera-Oyola & Daniela Grases & Marta Galvez-Viedma & Mustafa Sibai & Elena Satorres-Perez & Susana Lopez-Agullo & Rafael Badenes &, 2024. "Effect of aging on the human myometrium at single-cell resolution," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    8. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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