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新研究在单细胞水平上揭示系统性红斑狼疮异质性
2020-08-05 23:13

美国杰克逊实验室Jacques F. Banchereau、Virginia Pascual等研究人员合作在单细胞水平上揭示系统性红斑狼疮异质性。这一研究成果于2020年8月3日在线发表在国际学术期刊《自然—免疫学》上。

使用单细胞RNA测序,研究人员对33名患有不同程度疾病的系统性红斑狼疮(SLE)儿童和11位相匹配对照组的约276,000个外周血单核细胞进行了分析。干扰素刺激基因(ISG)的表达增加将SLE儿童的细胞与健康对照细胞区分开。高ISG表达特征(ISGhi)来自主要细胞类型中的少量转录定义亚群,包括单核细胞、CD4+和CD8+T细胞、天然杀伤细胞、常规和浆细胞样树突状细胞、B细胞,尤其是浆细胞。富含ISG和/或单基因狼疮相关基因独特亚群的扩增将疾病活性最高的患者分类。
 
对SLE成人患者的约82,000个单个外周血单核细胞进行分析,证实了具有最高疾病活性患者中类似亚群的扩增。这项研究为解决SLE转录特征的起源并为疾病异质性的精准医疗奠定了基础。
 
据悉,系统性红斑狼疮(SLE)患者显示出复杂的血液转录组,其细胞起源难以分辨。
 
附:英文原文

Title: Mapping systemic lupus erythematosus heterogeneity at the single-cell level

Author: Djamel Nehar-Belaid, Seunghee Hong, Radu Marches, Guo Chen, Mohan Bolisetty, Jeanine Baisch, Lynnette Walters, Marilynn Punaro, Robert J. Rossi, Cheng-Han Chung, Richie P. Huynh, Prashant Singh, William F. Flynn, Joy-Ann Tabanor-Gayle, Navya Kuchipudi, Asuncion Mejias, Magalie A. Collet, Anna Lisa Lucido, Karolina Palucka, Paul Robson, Santhanam Lakshminarayanan, Octavio Ramilo, Tracey Wright, Virginia Pascual, Jacques F. Banchereau

Issue&Volume: 2020-08-03

Abstract: Patients with systemic lupus erythematosus (SLE) display a complex blood transcriptome whose cellular origin is poorly resolved. Using single-cell RNA sequencing, we profiled ~276,000 peripheral blood mononuclear cells from 33 children with SLE with different degrees of disease activity and 11 matched controls. Increased expression of interferon-stimulated genes (ISGs) distinguished cells from children with SLE from healthy control cells. The high ISG expression signature (ISGhi) derived from a small number of transcriptionally defined subpopulations within major cell types, including monocytes, CD4+ and CD8+ T cells, natural killer cells, conventional and plasmacytoid dendritic cells, B cells and especially plasma cells. Expansion of unique subpopulations enriched in ISGs and/or in monogenic lupus-associated genes classified patients with the highest disease activity. Profiling of ~82,000 single peripheral blood mononuclear cells from adults with SLE confirmed the expansion of similar subpopulations in patients with the highest disease activity. This study lays the groundwork for resolving the origin of the SLE transcriptional signatures and the disease heterogeneity towards precision medicine applications. Banchereau and colleagues provide a resource dataset that examines disease-related transcriptional profiles of peripheral whole-blood cells from adolescent patients with SLE by single-cell RNA-seq analysis.

DOI: 10.1038/s41590-020-0743-0

Source: https://www.nature.com/articles/s41590-020-0743-0

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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