2022年5月26日，英国威康桑格研究所Gosia Trynka课题组在《自然—遗传学》杂志发表论文，揭示免疫疾病风险变异体在CD4⁺T细胞激活期间调节基因表达动态。

研究人员利用单细胞转录组学绘制了基因表达的影响（表达定量性状位点，eQTL）。研究人员对655,349个CD4⁺T细胞进行了分析，捕捉了119个健康人中未受刺激细胞的转录状态和细胞激活的三个时间点。这确定了38个细胞集群，包括只在激活的个别时间点出现的短暂集群。研究人员发现有6,407个基因的表达与遗传变异相关，其中2,265个（35%）在激活过程中受到动态调节。

此外，有127个基因受到与免疫介导的疾病相关的变异的调节，动态效应明显富集。这些结果强调了研究特定环境下的基因表达调控的重要性，并提供了对免疫介导疾病的遗传易感性机制的见解。

据悉，在激活过程中，T细胞经历了广泛的基因表达变化，塑造了细胞的特性以发挥其效应功能。了解这一过程的调控有助于解释遗传变异体如何容易导致免疫疾病。

附：英文原文

Title: Immune disease risk variants regulate gene expression dynamics during CD4+ T cell activation

Author: Soskic, Blagoje, Cano-Gamez, Eddie, Smyth, Deborah J., Ambridge, Kirsty, Ke, Ziying, Matte, Julie C., Bossini-Castillo, Lara, Kaplanis, Joanna, Ramirez-Navarro, Lucia, Lorenc, Anna, Nakic, Nikolina, Esparza-Gordillo, Jorge, Rowan, Wendy, Wille, David, Tough, David F., Bronson, Paola G., Trynka, Gosia

Issue&Volume: 2022-05-26

Abstract: During activation, T cells undergo extensive gene expression changes that shape the properties of cells to exert their effector function. Understanding the regulation of this process could help explain how genetic variants predispose to immune diseases. Here, we mapped genetic effects on gene expression (expression quantitative trait loci (eQTLs)) using single-cell transcriptomics. We profiled 655,349 CD4+ T cells, capturing transcriptional states of unstimulated cells and three time points of cell activation in 119 healthy individuals. This identified 38 cell clusters, including transient clusters that were only present at individual time points of activation. We found 6,407 genes whose expression was correlated with genetic variation, of which 2,265 (35%) were dynamically regulated during activation. Furthermore, 127 genes were regulated by variants associated with immune-mediated diseases, with significant enrichment for dynamic effects. Our results emphasize the importance of studying context-specific gene expression regulation and provide insights into the mechanisms underlying genetic susceptibility to immune-mediated diseases. Single-cell RNA sequencing of CD4+ naive and memory T cells from 119 individuals generates an expression quantitative trait locus (eQTL) map during T cell activation, identifying 6,407 eQTL genes, including 2,265 that are dynamically regulated.

DOI: 10.1038/s41588-022-01066-3

Source: https://www.nature.com/articles/s41588-022-01066-3