美国加州大学旧金山分校Chun Jimmie Ye和美国加州大学洛杉矶分校Noah Zaitlen团队共同合作取得重要工作进展。他们通过单细胞RNA-seq揭示细胞类型特异性分子和遗传与狼疮的关系。该项研究成果
在这里，研究人员使用多重单细胞RNA测序 (mux-seq) 分析了超过 120 万个外周血单核细胞（162例，99例对照）。病例表现出单核细胞中1型干扰素刺激基因 (ISG) 的表达升高，与单核细胞ISG表达相关的初始CD4+ T 细胞减少，以及总体限制性细胞毒性GZMH+ CD8+ T细胞的扩增。细胞类型特异性表达特征预测了病例对照状态，并将患者分为两种分子亚型。研究人员整合密集的基因分型数据来绘制细胞类型特异性顺式表达数量性状基因座，并将SLE相关变体与细胞类型特异性表达联系起来。这些结果证明mux-seq是一种系统化的方法来表征细胞组成、识别转录特征和注释与SLE相关的遗传变异。
据了解，系统性红斑狼疮(SLE)是一种异质性自身免疫性疾病。对与SLE相关的循环免疫细胞类型和状态的了解仍然不完全。
附：英文原文
Title: Single-cell RNA-seq reveals cell type–specific molecular and genetic associations to lupus
Author: Richard K. Perez, M. Grace Gordon, Meena Subramaniam, Min Cheol Kim, George C. Hartoularos, Sasha Targ, Yang Sun, Anton Ogorodnikov, Raymund Bueno, Andrew Lu, Mike Thompson, Nadav Rappoport, Andrew Dahl, Cristina M. Lanata, Mehrdad Matloubian, Lenka Maliskova, Serena S. Kwek, Tony Li, Michal Slyper, Julia Waldman, Danielle Dionne, Orit Rozenblatt-Rosen, Lawrence Fong, Maria Dall’Era, Brunilda Balliu, Aviv Regev, Jinoos Yazdany, Lindsey A. Criswell, Noah Zaitlen, Chun Jimmie Ye
Issue&Volume: 2022-04-08
Abstract: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.2 million peripheral blood mononuclear cells (162 cases, 99 controls) with multiplexed single-cell RNA sequencing (mux-seq). Cases exhibited elevated expression of type 1 interferon–stimulated genes (ISGs) in monocytes, reduction of nave CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell type–specific expression features predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data to map cell type–specific cis–expression quantitative trait loci and to link SLE-associated variants to cell type–specific expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE.
DOI: abf1970
Source: https://www.science.org/doi/10.1126/science.abf1970