Single-cell gene expression patterns in lupus monocytes independently indicate disease activity, interferon and therapy.
Single-cell gene expression patterns in lupus monocytes independently indicate disease activity, interferon and therapy.
复制标题
狼疮单核细胞中的单细胞基因表达模式独立指示疾病活动、干扰素和治疗
DOI：
10.1136/lupus-2016-000202
复制
发表时间：
2017
影响因子：
3.9
通讯作者：
Niewold TB
中科院分区：
文献类型：
--
作者：
Jin Z;Fan W;Jensen MA;Dorschner JM;Bonadurer GF 3rd;Vsetecka DM;Amin S;Makol A;Ernste F;Osborn T;Moder K;Chowdhary V;Niewold TB
在混合细胞群体的基因表达研究中，重要的发现可以被掩盖。我们研究了SLE患者单核细胞中单细胞基因表达的临床和免疫学特征。从SLE患者和对照组中分离纯化单核细胞，用于单细胞基因表达检测。在单个经典型(CL)和非经典性(NCL)单核细胞中测量了一组与单核细胞相关的转录本。对CL和NCL单核细胞的分析表明，许多基因在SLE单核细胞中的表达率低于对照组。CL和NCL数据集的无监督分层聚类显示了来自SLE患者的与疾病活动性、I型干扰素(干扰素)和药物使用相关的独立细胞簇。因此，这些因素中的每一个都对单核细胞基因的表达产生了不同的影响，这些影响可以单独识别，并且一些基因与疾病活动独特相关。我们发现I型干扰素直接诱导的基因与其他非干扰素诱导的基因之间存在细胞内相关性，提示I型干扰素在单个人SLE单核细胞中的下游生物学效应不同于CLS和NCLS。总之，单核细胞中单细胞基因的表达与SLE的一系列临床和生物学特征有关，比以前的混合细胞群体研究提供了更多的细节和对疾病背后的细胞生物学的洞察。
Important findings can be masked in gene expression studies of mixed cell populations. We examined single-cell gene expression in SLE patient monocytes in the context of clinical and immunological features. Monocytes were purified from patients with SLE and controls, and individually isolated for single-cell gene expression measurement. A panel of monocyte-related transcripts were measured in individual classical (CL) and non-classical (NCL) monocytes. Analyses of both CL and NCL monocytes demonstrated that many genes had a lower expression rate in SLE monocytes than in controls. Unsupervised hierarchical clustering of the CL and NCL data sets demonstrated independent clusters of cells from the patients with SLE that were related to disease activity, type I interferon (IFN) and medication use. Thus, each of these factors exerted a different impact on monocyte gene expression that could be identified separately, and a number of genes correlated uniquely with disease activity. We found within-cell correlations between genes directly induced by type I IFN-induced and other non–IFN-induced genes, suggesting the downstream biological effects of type I IFN in individual human SLE monocytes which differed between CLs and NCLs. In summary, single-cell gene expression in monocytes was associated with a wide range of clinical and biological features in SLE, providing much greater detail and insight into the cellular biology underlying the disease than previous mixed-cell population studies.