从克罗恩病队列中外周血单核细胞的多基因组图谱推断 B 细胞和 T 细胞的异质性一致性

Margaret Brown, Anne Dodd, Fang Shi, Emily Greenwood, Sini Nagpal, Vasantha L Kolachala, Subra Kugathasan, Greg Gibson
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引用次数: 0

摘要

背景和目的 克罗恩病的特征是由遗传、免疫和环境因素共同导致的胃肠道炎症。克罗恩病患者肠道组织的转录组学和表观基因组学分析揭示了有价值的病理学观点,但尚未对侵入性较小的外周血单核细胞(PBMCs)进行联合分析。此外,克罗恩病患者对治疗的不同反应意味着病理机制隐藏的多样性。方法 我们采用了单核多组学分析方法,将外周血单核细胞的 snRNA-seq 和 snATAC-seq 与多种开源生物信息学应用结合起来。结果 我们的研究结果揭示了个体间多种多样的转录特征,突显了 PBMC 特征的异质性。然而,在 B 细胞和 T 细胞中观察到了三个异质性群体之间惊人的一致性。不同的基因调控机制部分解释了这些特征,特别是在两个患有克罗恩病的个体中发现了涉及 TGFß 信号转导的特征。一个突变映射到了一个转录因子结合位点上,该位点位于一个与该通路表达相关的可访问差异峰上,这对以个性化方法了解疾病病理具有重要意义。结论 本研究强调了多组学分析如何揭示导致 PBMC 特征异质性的共同调控机制,其中一种机制可能是炎症性疾病所特有的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Concordant B and T Cell Heterogeneity Inferred from the Multiomic Landscape of Peripheral Blood Mononuclear Cells in a Crohn’s Disease Cohort
Background and Aims Crohn’s disease is characterized by inflammation in the gastrointestinal tract due to a combination of genetic, immune, and environmental factors. Transcriptomic and epigenomic profiling of intestinal tissue of Crohn’s disease patients have revealed valuable insights into pathology, however have not been conducted jointly on less invasive peripheral blood mononuclear cells (PBMCs). Furthermore, the heterogeneous responses to treatments among individuals with Crohn’s disease imply hidden diversity of pathological mechanisms. Methods We employed single nucleus multiomic analysis, integrating both snRNA-seq and snATAC-seq of PBMCs with a variety of open source bioinformatics applications. Results Our findings reveal a diverse range of transcriptional signatures among individuals, highlighting the heterogeneity in PBMC profiles. Nevertheless, striking concordance between three heterogeneous groups was observed across B cells and T cells. Differential gene regulatory mechanisms partially explain these profiles, notably including a signature involving TGFß signaling in two individuals with Crohn’s disease. A mutation mapped to a transcription factor binding site within a differentially accessible peak associated with the expression of this pathway, with implications for a personalized approach to understanding disease pathology. Conclusions This study highlights how multiomic analysis can reveal common regulatory mechanisms that underlie heterogeneity of PBMC profiles, one of which may be specific to inflammatory disease.
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