Single-cell eQTL analysis of activated T cell subsets reveals activation and cell type-dependent effects of disease-risk variants.
Single-cell eQTL analysis of activated T cell subsets reveals activation and cell type-dependent effects of disease-risk variants.
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DOI：
10.1126/sciimmunol.abm2508
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发表时间：
2022-02-25
影响因子：
24.8
通讯作者：
Vijayanand, Pandurangan
中科院分区：
文献类型：
--
作者：
Schmiedel, Benjamin J.;Gonzalez-Colin, Cristian;Fajardo, Vicente;Rocha, Job;Madrigal, Ariel;Ramirez-Suastegui, Ciro;Bhattacharyya, Sourya;Simon, Hayley;Greenbaum, Jason A.;Peters, Bjoern;Seumois, Gregory;Ay, Ferhat;Chandra, Vivek;Vijayanand, Pandurangan
遗传变异对在生物学相关背景下挑战的细胞的影响尚未得到充分探索。在这里，我们激活了来自89名健康受试者的CD 4 + T细胞，并使用> 100万个细胞进行了单细胞RNA-seq测定，以检查遗传变异的细胞类型特异性和激活依赖性效应。对19个不同的CD 4 + T细胞亚群的单细胞表达数量性状基因座（sc-eQTL）分析表明，超过4,000个基因的表达与常见的遗传多态性显著相关，并且这些基因中的大多数在特定细胞类型中表现出最突出的影响。这些基因包括许多编码对T细胞的活化、分化和效应子功能重要的分子的基因。我们还发现了从全基因组关联研究中鉴定的疾病风险变体的新基因关联，并强调了其影响最突出的细胞类型。我们发现，生物性别对CD 4 + T细胞亚群中的活化依赖性基因表达有重要影响。性别偏向的转录物显著富集在几个途径中，这些途径对于CD 4 + T细胞启动和执行效应子功能是必不可少的，如TCR信号传导、细胞因子、细胞因子受体、共刺激、凋亡和细胞-细胞粘附途径。总的来说，这个DICE（免疫细胞表达，eQTL和表观基因组学数据库）子项目突出了sc-eQTL研究的力量，可以同时探索常见遗传变异对基因表达的激活和细胞类型依赖性影响（https：dice-database.org）。与疾病风险相关的遗传变异表现出对免疫细胞中基因表达的激活和细胞类型依赖性影响。
The impact of genetic variants on cells challenged in biologically relevant contexts has not been fully explored. Here, we activated CD4+ T cells from 89 healthy subjects and performed a single-cell RNA-seq assay with > 1 million cells to examine cell-type-specific and activation-dependent effects of genetic variants. Single-cell expression quantitative trait loci (sc-eQTL) analysis of 19 distinct CD4+ T cell subsets showed that the expression of over 4,000 genes is significantly associated with common genetic polymorphisms, and that the majority of these genes show their most prominent effects in specific cell types. These genes included many that encode for molecules important for activation, differentiation and effector functions of T cells. We also discovered new gene associations for disease-risk variants identified from genome-wide association studies and highlighted the cell types in which their effects are most prominent. We found that biological sex has a major influence on activation-dependent gene expression in CD4+ T cell subsets. Sex-biased transcripts were significantly enriched in several pathways that are essential for the initiation and execution of effector functions by CD4+ T cells like TCR signaling, cytokines, cytokine receptors, co-stimulatory, apoptosis and cell-cell adhesion pathways. Overall, this DICE (Database of Immune Cell Expression, eQTLs, and Epigenomics) subproject highlights the power of sc-eQTL studies for simultaneously exploring the activation and cell-type-dependent effects of common genetic variants on gene expression (https://dice-database.org). Genetic variants associated with disease-risk manifest activation and cell-type-dependent effects on gene expression in immune cells.
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影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1126/science.aaa1578
发表时间：
2015-04-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ciancanelli MJ;Huang SX;Luthra P;Garner H;Itan Y;Volpi S;Lafaille FG;Trouillet C;Schmolke M;Albrecht RA;Israelsson E;Lim HK;Casadio M;Hermesh T;Lorenzo L;Leung LW;Pedergnana V;Boisson B;Okada S;Picard C;Ringuier B;Troussier F;Chaussabel D;Abel L;Pellier I;Notarangelo LD;García-Sastre A;Basler CF;Geissmann F;Zhang SY;Snoeck HW;Casanova JL
通讯作者：
Casanova JL
影响因子：
64.5
作者：
Hoffmann HH;Schneider WM;Rozen-Gagnon K;Miles LA;Schuster F;Razooky B;Jacobson E;Wu X;Yi S;Rudin CM;MacDonald MR;McMullan LK;Poirier JT;Rice CM
通讯作者：
Rice CM
影响因子：
16.6
作者：
Barbeira AN;Dickinson SP;Bonazzola R;Zheng J;Wheeler HE;Torres JM;Torstenson ES;Shah KP;Garcia T;Edwards TL;Stahl EA;Huckins LM;GTEx Consortium;Nicolae DL;Cox NJ;Im HK
通讯作者：
Im HK