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单细胞转录组学揭示了瘢痕疙瘩的细胞异质性及其侵袭性机制。

Single cell transcriptomics reveals the cellular heterogeneity of keloids and the mechanism of their aggressiveness.

作者信息

Cheng Xinwei, Gao Zhen, Shan Shengzhou, Shen Haoyu, Zheng Hongkun, Jin Lu, Li Qingfeng, Zhou Jia

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.

出版信息

Commun Biol. 2024 Dec 19;7(1):1647. doi: 10.1038/s42003-024-07311-1.

DOI:10.1038/s42003-024-07311-1
PMID:39702490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11659312/
Abstract

Keloid is a dermatofibrotic disease known for its aggressive nature and characterized by pathological scarring, which often leads to disfigurement and frequent recurrences. Effective therapies for keloids are still limited, presumably due to the inadequate comprehension of their aggressive mechanisms. In our study, we examined the unique scenario where both keloid and non-aggressive pathological scar originate from the same patient, providing a rare opportunity to explore the aggressive mechanisms of keloids through single-cell RNA sequencing. We found that the dominant fibroblast subgroup in keloids is mechanoresponsive group, which showed enhanced mechanotransduction and migration. This mechanoresponsive fibroblast subgroup is likely to be the key cell population and confer aggressive growth of keloids. The results also indicate that the endothelial cells and keratinocytes in keloid involve in endothelial-mesenchymal and epithelial-mesenchymal transitions. This study demonstrated the mechanoresponsive fibroblasts and multiple cellular mesenchymal processes could pave the way for further investigations into the keloid aggressiveness.

摘要

瘢痕疙瘩是一种以侵袭性为特征的皮肤纤维化疾病,其特点是病理性瘢痕形成,常导致毁容且频繁复发。瘢痕疙瘩的有效治疗方法仍然有限,这可能是由于对其侵袭机制的理解不足所致。在我们的研究中,我们研究了瘢痕疙瘩和非侵袭性病理性瘢痕均源自同一患者的独特情况,这为通过单细胞RNA测序探索瘢痕疙瘩的侵袭机制提供了难得的机会。我们发现,瘢痕疙瘩中占主导地位的成纤维细胞亚群是机械反应性群体,其显示出增强的机械转导和迁移能力。这个机械反应性成纤维细胞亚群可能是关键细胞群体,并赋予瘢痕疙瘩侵袭性生长。结果还表明,瘢痕疙瘩中的内皮细胞和角质形成细胞参与内皮-间充质转化和上皮-间充质转化。这项研究表明,机械反应性成纤维细胞和多个细胞间充质过程可为进一步研究瘢痕疙瘩的侵袭性铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/c940f6dd58b7/42003_2024_7311_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/b9ccfafdf698/42003_2024_7311_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/549ab66d1d71/42003_2024_7311_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/519ab2256aab/42003_2024_7311_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/60df066daf0d/42003_2024_7311_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/1eb4a59bcbd4/42003_2024_7311_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/c940f6dd58b7/42003_2024_7311_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/b9ccfafdf698/42003_2024_7311_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/549ab66d1d71/42003_2024_7311_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/519ab2256aab/42003_2024_7311_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/60df066daf0d/42003_2024_7311_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/1eb4a59bcbd4/42003_2024_7311_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40b5/11659312/c940f6dd58b7/42003_2024_7311_Fig6_HTML.jpg

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本文引用的文献

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Exp Dermatol. 2024 May;33(5):e15088. doi: 10.1111/exd.15088.
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Advances in single-cell RNA sequencing and its applications in cancer research.单细胞 RNA 测序技术的进展及其在癌症研究中的应用。
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The transcriptional profile of keloidal Schwann cells.瘢痕性施万细胞的转录谱。
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