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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1398767
This article is part of the Research Topic Advances in Understanding of Cell Types in Tissue Remodeling and Fibrosis View all 5 articles

Unraveling the role of CLOCK gene in fibrotic skin diseases: insights from single-cell RNA sequencing analysis

Provisionally accepted
Tang Rui Tang Rui 1*Li Yue Li Yue 2Li Changmin Li Changmin 2Liu qin Liu qin 3Gao tianbao Gao tianbao 3Liu wei Liu wei 2
  • 1 Southwest Hospital, Army Medical University, Chongqing, China
  • 2 Institute of Burn Research, Southwest Hospital, Army Medical University, Chongqing, China
  • 3 Bioinformatics Center, Third Military Medical University, Chongqing, China

The final, formatted version of the article will be published soon.

    Fibrosis, characterized by excessive extracellular matrix (ECM) accumulation and fibroblast proliferation, significantly contributes to global morbidity and mortality, affecting millions worldwide. Despite its prevalence, the mechanisms underlying fibrotic skin diseases remain poorly understood, and effective treatments are scarce. This study leverages single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of fibroblasts in fibrotic skin diseases, including normal skin, scar, keloid, and scleroderma. Through comprehensive analysis of scRNA-seq data from public repositories, we identified distinct fibroblast subpopulations specific to each fibrotic condition. Notably, pivotal regulators for each sub-fibroblast cluster were discovered: IRF4 for scar, CLOCK for keloid, RUNX3 for scleroderma, and HOXC4 for normal skin. Further, CLOCK was found to be predominantly expressed in keloid tissues, with its upregulation enhancing fibroblast proliferation and migration in vitro. Analysis of The Cancer Genome Atlas (TCGA) data revealed that CLOCK and its regulon genes were upregulated in skin cutaneous melanoma and even more so in metastatic tumors. Our findings underscore the utility of scRNA-seq in dissecting the cellular complexity of fibrotic skin diseases and highlight potential therapeutic targets. This study not only advances our understanding of fibroblast heterogeneity in fibrosis but also opens avenues for targeted therapeutic strategies, moving closer to personalized medicine for fibrotic diseases.

    Keywords: Fibrosis, Fibroblast heterogeneity, single-cell RNA sequencing, clock, Migration

    Received: 12 Mar 2024; Accepted: 06 Aug 2024.

    Copyright: © 2024 Rui, Yue, Changmin, qin, tianbao and wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tang Rui, Southwest Hospital, Army Medical University, Chongqing, 400038, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.