关键词: Crohn's disease cellular heterogeneity fibroblasts single‐cell RNA sequencing ustekinumab treatment

Mesh : Crohn Disease / genetics drug therapy Humans Ustekinumab / therapeutic use Single-Cell Analysis / methods Gene Expression Profiling / methods Protein Interaction Maps Fibroblasts / metabolism Biomarkers Female Transcriptome Adult Male T-Lymphocytes / metabolism immunology Treatment Outcome Sequence Analysis, RNA / methods Gene Regulatory Networks

来  源:   DOI:10.1002/jgm.3715

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.
摘要:
背景:本研究旨在使用单细胞RNA测序来剖析克罗恩病(CD)的细胞复杂性,专注于识别炎症组织中的关键细胞群及其转录谱。
方法:我们应用scRNA测序来比较CD患者与健康对照的细胞组成,利用Seurat进行聚类和注释。构建差异基因表达分析和蛋白质-蛋白质相互作用网络以识别关键基因和途径。
结果:我们的研究确定了CD中八种不同的细胞类型,强调关键的成纤维细胞和T细胞相互作用。分析揭示了关键的细胞通讯,并确定了与疾病病理有关的重要基因和途径。成纤维细胞的作用通过在患病样品中的高表达强调,提供对疾病机制和潜在治疗目标的见解,包括对ustekinumab治疗的反应,从而在分子水平上丰富了我们对CD的理解。
结论:我们的发现强调了CD中复杂的细胞和分子相互作用,提出新的生物标志物和治疗靶点,提供对疾病机制和治疗意义的见解。
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