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单细胞 RNA 测序揭示银屑病中角质形成细胞和成纤维细胞的异质性及其通过上皮-间充质转化的相互作用。

Single-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis.

机构信息

Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Department of Biochemistry and Molecular Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan, Shandong, China.

出版信息

Cell Death Dis. 2024 Mar 12;15(3):207. doi: 10.1038/s41419-024-06583-z.

DOI:10.1038/s41419-024-06583-z
PMID:38472183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10933286/
Abstract

The pathogenesis of psoriasis, a chronic inflammatory autoimmune skin disease with a high global prevalence, remains unclear. We performed a high-resolution single-cell RNA sequencing analysis of 94,759 cells from 13 samples, including those from psoriasis model mice and wild-type mice. We presented a single-cell atlas of the skin of imiquimod-induced mice with psoriasis and WT mice, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial-mesenchymal transition and validated the results with drug verification. Moreover, we conducted a tentative exploration of the potential pathways involved and revealed that the IL-17 signalling pathway may be the most relevant pathway. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.

摘要

银屑病是一种慢性炎症性自身免疫性皮肤病,全球发病率很高,但发病机制尚不清楚。我们对 13 个样本(包括银屑病模型小鼠和野生型小鼠)的 94759 个细胞进行了高分辨率单细胞 RNA 测序分析。我们展示了咪喹莫特诱导的银屑病小鼠和 WT 小鼠皮肤的单细胞图谱,特别是角质形成细胞和成纤维细胞的异质性。更有趣的是,我们发现特殊的角质形成细胞亚型和成纤维细胞亚型可以通过上皮-间充质转化相互作用,并通过药物验证验证了结果。此外,我们对潜在的相关途径进行了初步探索,揭示了 IL-17 信号通路可能是最相关的途径。总的来说,我们揭示了与银屑病相关的关键细胞的全周期景观,并对银屑病的发病机制有了更全面的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/062f71901880/41419_2024_6583_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/bd5210392111/41419_2024_6583_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/a4afd9bb774c/41419_2024_6583_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/ead0ae41ebb6/41419_2024_6583_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/29db07bd1275/41419_2024_6583_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/187b01bff850/41419_2024_6583_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/6c823df99964/41419_2024_6583_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/4455499e3dc2/41419_2024_6583_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/062f71901880/41419_2024_6583_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/bd5210392111/41419_2024_6583_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/a4afd9bb774c/41419_2024_6583_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/109551e52e2b/41419_2024_6583_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/ead0ae41ebb6/41419_2024_6583_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/29db07bd1275/41419_2024_6583_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/187b01bff850/41419_2024_6583_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/6c823df99964/41419_2024_6583_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/4455499e3dc2/41419_2024_6583_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31fc/10933286/062f71901880/41419_2024_6583_Fig9_HTML.jpg

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