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 M. Guimaraes,
Alina Ulezko Antonova,
Tian Qiu,
Sanja Sviben,
Gregory Strout,
James A.J. Fitzpatrick,
Yun Chen,
Susan Gilfillan,
Do-Hyun Kim,
Steven J. Van Dyken,
Maxim N. Artyomov,
Marco Colonna
Affiliations
Jinchao Hou
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Yingyue Zhou
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Zhangying Cai
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Marina Terekhova
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Amanda Swain
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Prabhakar S. Andhey
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Rafaela M. Guimaraes
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Ribeirão Preto Medical School, University of São Paulo - Ribeirão Preto, São Paulo 14049-900, Brazil
Alina Ulezko Antonova
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Tian Qiu
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA
Sanja Sviben
Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110, USA
Gregory Strout
Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110, USA
James A.J. Fitzpatrick
Washington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110, USA; Departments of Cell Biology and Physiology and Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110, USA
Yun Chen
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA
Susan Gilfillan
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Do-Hyun Kim
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Steven J. Van Dyken
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Maxim N. Artyomov
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Marco Colonna
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
Summary: 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 MAFBhi 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.
