JAK/STAT 信号转导促进了溃疡性结肠炎独特细胞状态的出现。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-18 DOI:10.1016/j.stemcr.2024.06.006
Grzegorz Maciag, Stine Lind Hansen, Kata Krizic, Lauge Kellermann, Maureen Joy Inventor Zøylner, Svetlana Ulyanchenko, Martti Maimets, Astrid Møller Baattrup, Lene Buhl Riis, Konstantin Khodosevich, Toshiro Sato, Raul Bardini Bressan, Ole Haagen Nielsen, Kim B Jensen
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引用次数: 0

摘要

肠上皮可确保吸收重要的营养物质,并充当管腔内容物和底层免疫系统之间的屏障。在溃疡性结肠炎(UC)等炎症性肠病中,这一屏障受到破坏,患者会出现令人衰弱的症状。在这里,我们对上皮细胞进行了单细胞 RNA 分析,并概述了健康人和 UC 患者的细胞命运决定模式。我们证明了 UC 患者的分层行为模式发生了改变,并确定了结肠上皮溃疡区和非溃疡区与 Janus 激酶/信号转导和激活转录(JAK/STAT)激活相关的独特细胞状态。这些转录变化可以在人类结肠器官组织中再现,其中细胞因子介导的 JAK/STAT 激活导致了具有增强再生特性的细胞群的出现。总之,我们的研究结果表明,在人类上皮组织再生过程中,上皮细胞和细胞因子信号转导之间错综复杂的关系调节着细胞的命运,这对理解 UC 生物学具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
JAK/STAT signaling promotes the emergence of unique cell states in ulcerative colitis.

The intestinal epithelium ensures uptake of vital nutrients and acts as a barrier between luminal contents and the underlying immune system. In inflammatory bowel diseases, such as ulcerative colitis (UC), this barrier is compromised, and patients experience debilitating symptoms. Here, we perform single-cell RNA profiling of epithelial cells and outline patterns of cell fate decisions in healthy individuals and UC patients. We demonstrate that patterns of hierarchical behavior are altered in UC patients and identify unique cellular states associated with Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation in ulcerated and non-ulcerated areas of the colonic epithelium. These transcriptional changes could be recapitulated in human colonic organoids, wherein cytokine-mediated activation of JAK/STAT led to the emergence of cell populations with augmented regenerative properties. Altogether, our findings indicate that intricate relationships between epithelial and cytokine signaling regulate cell fate during epithelial tissue regeneration in humans and have important implications for the understanding of UC biology.

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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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