当前位置: X-MOL 学术Nature › 论文详情
MAFG-driven astrocytes promote CNS inflammation
Nature ( IF 43.070 ) Pub Date : 2020-02-12 , DOI: 10.1038/s41586-020-1999-0
Michael A. Wheeler; Iain C. Clark; Emily C. Tjon; Zhaorong Li; Stephanie E. J. Zandee; Charles P. Couturier; Brianna R. Watson; Giulia Scalisi; Sarah Alkwai; Veit Rothhammer; Assaf Rotem; John A. Heyman; Shravan Thaploo; Liliana M. Sanmarco; Jiannis Ragoussis; David A. Weitz; Kevin Petrecca; Jeffrey R. Moffitt; Burkhard Becher; Jack P. Antel; Alexandre Prat; Francisco J. Quintana

Multiple sclerosis is a chronic inflammatory disease of the CNS1. Astrocytes contribute to the pathogenesis of multiple sclerosis2, but little is known about the heterogeneity of astrocytes and its regulation. Here we report the analysis of astrocytes in multiple sclerosis and its preclinical model experimental autoimmune encephalomyelitis (EAE) by single-cell RNA sequencing in combination with cell-specific Ribotag RNA profiling, assay for transposase-accessible chromatin with sequencing (ATAC–seq), chromatin immunoprecipitation with sequencing (ChIP–seq), genome-wide analysis of DNA methylation and in vivo CRISPR–Cas9-based genetic perturbations. We identified astrocytes in EAE and multiple sclerosis that were characterized by decreased expression of NRF2 and increased expression of MAFG, which cooperates with MAT2α to promote DNA methylation and represses antioxidant and anti-inflammatory transcriptional programs. Granulocyte–macrophage colony-stimulating factor (GM-CSF) signalling in astrocytes drives the expression of MAFG and MAT2α and pro-inflammatory transcriptional modules, contributing to CNS pathology in EAE and, potentially, multiple sclerosis. Our results identify candidate therapeutic targets in multiple sclerosis.
更新日期:2020-02-13

 

全部期刊列表>>
化学/材料学中国作者研究精选
Springer Nature 2019高下载量文章和章节
《科学报告》最新环境科学研究
ACS材料视界
自然科研论文编辑服务
中南大学国家杰青杨华明
剑桥大学-
中国科学院大学化学科学学院
材料化学和生物传感方向博士后招聘
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug