Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination

被引:29
|
作者
Hou, Jinchao [1 ]
Zhou, Yingyue [1 ]
Cai, Zhangying [1 ]
Terekhova, Marina [1 ]
Swain, Amanda [1 ,9 ]
Andhey, Prabhakar S. [1 ]
Guimaraes, Rafaela M. [1 ,2 ]
Antonova, Alina Ulezko [1 ]
Qiu, Tian [3 ]
Sviben, Sanja [4 ]
Strout, Gregory [4 ]
Fitzpatrick, James A. J. [4 ,5 ,6 ,7 ]
Chen, Yun [1 ,8 ]
Gilfillan, Susan [1 ]
Kim, Do-Hyun [1 ]
Van Dyken, Steven J. [1 ]
Artyomov, Maxim N. [1 ]
Colonna, Marco [1 ]
机构
[1] Washington Univ Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[2] Univ Sao Paulo Ribeirao Preto, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP, Brazil
[3] Washington Univ Sch Med, Dept Genet, St Louis, MO 63110 USA
[4] Washington Univ Sch Med, Washington Univ Ctr Cellular Imaging, St Louis, MO 63110 USA
[5] Washington Univ Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA
[6] Washington Univ Sch Med, Dept Neurosci, St Louis, MO 63110 USA
[7] Washington Univ St Louis, Dept Biomed Engn, St Louis, MO 63110 USA
[8] Washington Univ Sch Med, Dept Neurol, St Louis, MO 63110 USA
[9] 10X Genom, Pleasanton, CA 94588 USA
来源
CELL REPORTS | 2023年 / 42卷 / 04期
基金
巴西圣保罗研究基金会; 美国国家卫生研究院;
关键词
PROMOTES REMYELINATION; UP-REGULATION; WHITE-MATTER; CUPRIZONE; MYELINATION; ACTIVATION; MICROGLIA; MODEL; GLIA; DIFFERENTIATION;
D O I
10.1016/j.celrep.2023.112293
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies, and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination and remyelination occurring in these diseases. Here, we present a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells in this model. We define demyelination-associated oligodendrocytes (DOLs) and remyelination-associated MAFB(hi) microglia, as well as astrocytes and vascular cells with signatures of altered metabolism, oxidative stress, and interferon response. Furthermore, snRNA-seq provides insights into how brain cell types connect and interact, defining complex circuitries that impact demyelination and remyelination. As an explicative example, perturbation of microglia caused by TREM2 deficiency indirectly impairs the induction of DOLs. Altogether, this study provides a rich resource for future studies investigating mechanisms underlying demyelinating diseases.
引用
收藏
页数:25
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