Single-cell sequencing combined with spatial transcriptomics reveals the characteristics of follicle-targeted inflammation patterns in primary cicatricial alopecia.

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Qitao Chen, Yuqian Li, Qilin Zhu, Zhongming Li, Guanghui Shao, Yanjun Liu, Peixuan Jiang, Qiuwei Tao, Lili Shen, Jing Zhu, Linwei Wei, Yanhua Li, Xufeng Du
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引用次数: 0

Abstract

Background: Primary cicatricial alopecia (PCA) causes irreversible hair loss due to immune-mediated hair follicle destruction. This study investigates follicle-targeted inflammation in lichen planopilaris (LPP), a major PCA subtype, to identify therapeutic targets.

Methods: Scalp samples from LPP, localized scleroderma (LS), and controls were analyzed using single-cell RNA sequencing and spatial transcriptomics. Cellular composition, spatial localization, and intercellular interactions were examined using differential gene expression and ligand-receptor analyses.

Results: CD8⁺ effector memory T cells (Tem) and macrophages infiltrated hair follicles in LPP, disrupting immune privilege and promoting scarring. Heightened interferon-γ (IFN-γ) signaling and STAT1 activation in Tem cells caused epithelial-mesenchymal transition (EMT) in hair follicle stem cells (HFSCs). Additionally, macrophage-secreted oncostatin M (OSM) impaired HFSC integrity. These mechanisms drive LPP's inflammation and fibrosis.

Conclusions: Our findings identify interferon-γ and oncostatin M as key drivers of LPP pathogenesis, offering targets to reduce follicular scarring and preserve hair growth.

Trial registration: Not applicable.

单细胞测序结合空间转录组学揭示了原发性瘢痕性脱发中毛囊靶向炎症模式的特征。
背景:原发性瘢痕性脱发(PCA)由于免疫介导的毛囊破坏导致不可逆的脱发。本研究研究了扁平苔藓(LPP)的滤泡靶向炎症,这是一种主要的PCA亚型,以确定治疗靶点。方法:采用单细胞RNA测序和空间转录组学对LPP、局限性硬皮病(LS)和对照组的头皮样本进行分析。通过差异基因表达和配体受体分析,研究了细胞组成、空间定位和细胞间相互作用。结果:CD8 +效应记忆T细胞(Tem)和巨噬细胞浸润LPP毛囊,破坏免疫特权,促进瘢痕形成。在毛囊干细胞(HFSCs)中,干扰素-γ (IFN-γ)信号和STAT1激活的升高引起了上皮-间充质转化(EMT)。此外,巨噬细胞分泌的抑癌素M (OSM)损害了HFSC的完整性。这些机制驱动LPP的炎症和纤维化。结论:我们的研究结果确定干扰素-γ和肿瘤抑制素M是LPP发病机制的关键驱动因素,为减少毛囊瘢痕形成和保持头发生长提供了靶点。试验注册:不适用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell and Bioscience
Cell and Bioscience BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
10.70
自引率
0.00%
发文量
187
审稿时长
>12 weeks
期刊介绍: Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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