Single-cell analysis of Crohn's disease: Unveiling heterogeneity and evaluating ustekinumab outcomes

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-07-04 DOI:10.1002/jgm.3715

Zheng-Yang Li, Yong-Hong Sun, Qian-Hua, Hai-Yan Wang, Ya-Jie Wang, Miao-Jiang

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引用次数: 0

Abstract

Background

The present study aimed to dissect the cellular complexity of Crohn's disease (CD) using single-cell RNA sequencing, focusing on identifying key cell populations and their transcriptional profiles in inflamed tissue.

Methods

We applied scRNA-sequencing to compare the cellular composition of CD patients with healthy controls, utilizing Seurat for clustering and annotation. Differential gene expression analysis and protein–protein interaction networks were constructed to identify crucial genes and pathways.

Results

Our study identified eight distinct cell types in CD, highlighting crucial fibroblast and T cell interactions. The analysis revealed key cellular communications and identified significant genes and pathways involved in the disease's pathology. The role of fibroblasts was underscored by elevated expression in diseased samples, offering insights into disease mechanisms and potential therapeutic targets, including responses to ustekinumab treatment, thus enriching our understanding of CD at a molecular level.

Conclusions

Our findings highlight the complex cellular and molecular interplay in CD, suggesting new biomarkers and therapeutic targets, offering insights into disease mechanisms and treatment implications.

Abstract Image

查看原文本刊更多论文

克罗恩病的单细胞分析：揭示异质性并评估乌司替尼的疗效。

背景：本研究旨在利用单细胞RNA测序技术剖析克罗恩病（CD）的细胞复杂性，重点是确定炎症组织中的关键细胞群及其转录特征：我们采用scRNA测序技术比较了CD患者和健康对照组的细胞组成，并利用Seurat进行了聚类和注释。结果：我们的研究在 CD 患者和健康对照组中发现了八种不同的细胞类型：结果：我们的研究确定了 CD 中八种不同的细胞类型，突出了成纤维细胞和 T 细胞之间的重要相互作用。分析揭示了关键的细胞通讯，并确定了参与疾病病理的重要基因和通路。成纤维细胞在患病样本中的表达升高凸显了成纤维细胞的作用，为疾病机制和潜在治疗靶点（包括对乌司替尼治疗的反应）提供了见解，从而丰富了我们对CD在分子水平上的认识：我们的研究结果突显了CD中复杂的细胞和分子相互作用，提出了新的生物标记物和治疗靶点，为疾病机制和治疗意义提供了新的视角。

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

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.