Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination
Jinchao Hou, Yingyue Zhou, Zhangying Cai, Marina Terekhova, Amanda Swain, Prabhakar S. Andhey, Rafaela Mano Guimarães, Alina Ulezko Antonova, Tian Qiu, Sanja Sviben, Gregory W. Strout, James A. J. Fitzpatrick, Yun Chen, Susan Gilfillan, DoHyun Kim, Steven J. Van Dyken, Maxim N. Artyomov, Marco Colonna
Abstract
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.