ArticleActa neuropathologica2023
From methylation to myelination: epigenomic and transcriptomic profiling of chronic inactive demyelinated multiple sclerosis lesions.
Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- CRISPR and Myelin regeneration: a systematic review of applications in demyelinating CNS Disorders, with a focus on MS.Regenerative medicine · 2025Pooled it
- Article
- Early oligodendrocyte dysfunction signature in Alzheimer's disease: Insights from DNA methylomics and transcriptomics.Molecular psychiatry · 2026Article
- Integrative epigenomic landscape of Alzheimer's Disease brains reveals oligodendrocyte molecular perturbations associated with tau.Nature communications · 2026Article
- Review
- Application potential of induced pluripotent stem cells in the research and treatment of autoimmune diseases (Review).Molecular medicine reports · 2025Review
- NLRC5-Mediated Epigenetic and Proteomic Regulation of Microglial Panoptosis Drives Neuroinflammation in Multiple Sclerosis.Molecular neurobiology · 2025Article
- Platelets During Myelin Repair in Multiple Sclerosis: Friend or Foe?Journal of neurochemistry · 2025Review
- The Neuropsychology of Chronic Neurological Disorders: A Review of Cognitive and Emotional Impairments.Cureus · 2025Review
- From Molecules to Models: miRNAs and Advanced Human Platforms of Neurodegeneration and Repair in Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Systematic Analysis of Alternative Splicing in Transcriptomes of Multiple Sclerosis Patient Brain Samples.International journal of molecular sciences · 2025Article
- Epigenetic and Mitochondrial Metabolic Dysfunction in Multiple Sclerosis: A Review of Herbal Drug Approaches and Current Clinical Trials.Molecular neurobiology · 2025Review
- Article
- The Impact of HIV on Early Brain Aging-A Pathophysiological (Re)View.Journal of clinical medicine · 2024Review
- A Comprehensive Examination of the Role of Epigenetic Factors in Multiple Sclerosis.International journal of molecular sciences · 2024Review
- The Impact of Sample Storage on Blood Methylation: Towards Assessing Myelin Gene Methylation as a Biomarker for Progressive Multiple Sclerosis.International journal of molecular sciences · 2024Article
- Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review.Immunity, inflammation and disease · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 5 countries.
Funding
Abstract
In the progressive phase of multiple sclerosis (MS), the hampered differentiation capacity of oligodendrocyte precursor cells (OPCs) eventually results in remyelination failure. We have previously shown that DNA methylation of Id2/Id4 is highly involved in OPC differentiation and remyelination. In this study, we took an unbiased approach by determining genome-wide DNA methylation patterns within chronically demyelinated MS lesions and investigated how certain epigenetic signatures relate to OPC differentiation capacity. We compared genome-wide DNA methylation and transcriptional profiles between chronically demyelinated MS lesions and matched normal-appearing white matter (NAWM), making use of post-mortem brain tissue (n = 9/group). DNA methylation differences that inversely correlated with mRNA expression of their corresponding genes were validated for their cell-type specificity in laser-captured OPCs using pyrosequencing. The CRISPR-dCas9-DNMT3a/TET1 system was used to epigenetically edit human-iPSC-derived oligodendrocytes to assess the effect on cellular differentiation. Our data show hypermethylation of CpGs within genes that cluster in gene ontologies related to myelination and axon ensheathment. Cell type-specific validation indicates a region-dependent hypermethylation of MBP, encoding for myelin basic protein, in OPCs obtained from white matter lesions compared to NAWM-derived OPCs. By altering the DNA methylation state of specific CpGs within the promotor region of MBP, using epigenetic editing, we show that cellular differentiation and myelination can be bidirectionally manipulated using the CRISPR-dCas9-DNMT3a/TET1 system in vitro. Our data indicate that OPCs within chronically demyelinated MS lesions acquire an inhibitory phenotype, which translates into hypermethylation of crucial myelination-related genes. Altering the epigenetic status of MBP can restore the differentiation capacity of OPCs and possibly boost (re)myelination.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.