Researchers construct a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cell

This paper by co-first authors JinChao Hou, PhD, and Yingyue Zhou, PhD, postdoctoral researchers in the Colonna Lab WUSTL, presents a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells during demyelination and remyelination induced by cuprizone, a copper chelator widely used to simulate demyelination occurring in MS and neurodegenerative diseases.

Myelin is a multilayered lipid sheath produced by oligodendrocytes (OLs) that wrap around neuronal axons to facilitate the propagation of electrical impulses in the white matter of central nervous system. Patients with multiple sclerosis (MS), leukoencephalopathies, cerebral vasculopathies, and neurodegenerative diseases including Alzheimer’s disease show a loss of myelin sheaths or demyelination, leading to axon degeneration and impairment of neuronal connectivity and functions.

The underlying mechanism of demyelination is still unclear. It’s possible that immune system attacks the myelin sheath at least in certain diseases. Understanding of the behavior of all brain cells in response to myelin damage could be key in developing new therapies that stave off demyelination or help repair the myelin sheath.

In the Cell Reports paper, Dr. Hou, Dr. Zhou and team identify key transcriptional signatures of brain astrocytes and vascular cells, defining metabolic, anti-oxidative, and interferon signatures; a special state of microglia during remyelination that is induced by the transcription factor MAFB; and a population of demyelination-associated oligodendrocytes that is dependent on the receptor of TREM2.

“Our study provides a rich resource for future studies investigating how therapies can improve the function of astrocytes, OLs, microglia, and vascular cells during demyelination, and facilitate myelin repair,” the team said.

Availability – Single-nucleus RNA-seq data have been deposited at the Gene Expression Omnibus (GEO) database

Hou J, Zhou Y, Cai Z, Terekhova M, Swain A, Andhey PS, Guimaraes RM, Ulezko Antonova A, Qiu T, Sviben S, Strout G, Fitzpatrick JAJ, Chen Y, Gilfillan S, Kim DH, Van Dyken SJ, Artyomov MN, Colonna M. (2023) Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination. Cell Rep 42(4):112293. [article]

Leave a Reply

Your email address will not be published. Required fields are marked *

*

Time limit is exhausted. Please reload CAPTCHA.