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Updated: Jul 25, 2025
Simultaneous Isolation of Principal Central Nervous System-Resident Cell Types from Adult Autoimmune Encephalomyelitis Mice
Published on: October 6, 2023
Nanopore sequencing identifies differentially methylated genes in the central nervous system in experimental
Wen Si1, Ying Ni1, Qianling Jiang1
1Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, SAR 999077, China.
Abstract:
Multiple Sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS) that might be triggered by aberrant epigenetic changes in the genome. DNA methylation is the most studied epigenetic mechanism that participates in MS pathogenesis. However, the overall methylation level in the CNS of MS patients remains elusive. We used direct long-read nanopore DNA sequencing and characterized the differentially methylated genes in the brain from mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We identified 163 hypomethylated promoters and 327 hypermethylated promoters. These genomic alterations were linked to various biological processes including metabolism, immune responses, neural activities, and mitochondrial dynamics, all of which are vital for EAE development. Our results indicate a great potential of nanopore sequencing in identifying genomic DNA methylation in EAE and provide important guidance for future studies investigating the MS/EAE pathology.
Insights
Aberrant DNA methylation in the central nervous system (CNS) may trigger multiple sclerosis (MS). Nanopore sequencing revealed significant promoter methylation changes in an MS animal model, impacting key biological processes.
Area of Science:
- Neuroimmunology
- Epigenetics
- Genomics
Background:
- Multiple Sclerosis (MS) is a chronic CNS autoimmune disease potentially driven by epigenetic alterations.
- DNA methylation is a key epigenetic mechanism implicated in MS pathogenesis, but its overall level in the CNS is not well understood.
Purpose of the Study:
- To investigate genome-wide DNA methylation patterns in the brain of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
- To identify differentially methylated genes and their associated biological pathways in EAE.
Main Methods:
- Direct long-read nanopore DNA sequencing was employed to profile DNA methylation in the EAE mouse brain.
- Bioinformatic analysis was used to identify hypomethylated and hypermethylated promoters.
Main Results:
- 163 hypomethylated and 327 hypermethylated promoters were identified in the EAE mouse brain.
- These methylation changes were associated with critical biological processes including metabolism, immune responses, neural activity, and mitochondrial dynamics.
Conclusions:
- Nanopore sequencing is a powerful tool for identifying genomic DNA methylation in EAE.
- The identified methylation alterations provide insights into MS/EAE pathology and suggest potential therapeutic targets.
