Transcriptomic, epigenetic and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus [scRNA-seq]. Transcriptomic, epigenetic and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus [scRNA-seq]

Two subpopulations of low density granulocytes (LGDs) were defined in terms of different gene expression patterns, transcriptional and epigenetic features as well as functions. This study provides insights into the mechanism of immune dysregulation and the vascular damage characteristic of lupus. Overall design: This dataset includes 3 scRNA samples, which belong to the super series GSE139360. Transcriptomics and epigenetic assessment of lupus PBMCs, LDGs, autologous normal-density neutrophils (NDN) and healthy control (HC) neutrophils was performed by mRNA sequencing, single cell RNAseq and assay for transposase-accessible chromatin sequencing. NET formation, chemotaxis, phagocytosis, degranulation, induction of endothelial dysfunction and release of oxidized nucleic acids were compared among subsets.

本研究依据不同的基因表达模式、转录及表观遗传特征与功能，对低密度粒细胞（low density granulocytes, LGDs）的两个亚群进行了界定。本研究为狼疮（lupus）的免疫失调机制与特征性血管损伤提供了新的见解。实验设计概述：本数据集包含3个单细胞RNA测序样本，隶属于超级系列数据集GSE139360。本研究通过mRNA测序、单细胞RNA测序及转座酶可及性染色质测序（assay for transposase-accessible chromatin sequencing），对狼疮患者外周血单个核细胞（peripheral blood mononuclear cell, PBMC）、低密度粒细胞（low density granulocytes, LDGs）、自体正常密度中性粒细胞（normal-density neutrophils, NDN）以及健康对照（healthy control, HC）中性粒细胞开展了转录组学与表观遗传学分析。研究人员对各亚群的中性粒细胞胞外陷阱（neutrophil extracellular traps, NETs）形成能力、趋化活性、吞噬功能、脱颗粒作用、内皮功能障碍诱导能力以及氧化核酸释放水平进行了对比分析。