Evidence map›Paper›PMID 41075785›Full record

ArticleNeuron2025

Integrated omics reveals disease-associated radial glia-like cells with epigenetically dysregulated interferon response in multiple sclerosis.

Bongsoo Park, Alexandra M Nicaise, Dimitrios Tsitsipatis, Liviu Pirvan, Daniel Zucha, Andi Munteanu, Pranathi Prasad, Miguel Larraz Lopez De Novales, Cristian Bulgaru, Rafael Kollyfas and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors.

Bongsoo ParkEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Alexandra M NicaiseDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK. Electronic address: an574@cam.ac.uk.
Dimitrios TsitsipatisComputational Biology and Genomics Core, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Liviu PirvanCambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
Daniel ZuchaLaboratory of Glial Biology and Omics Technologies, Institute of Biotechnology of the Czech Academy of Sciences, 25250 Vestec, Czech Republic; Department of Informatics and Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, 16000 Prague , Czech Republic.
Andi MunteanuCambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK; Faculty of Computer Science, Alexandru Ioan University, Iasi, Romania.
Pranathi PrasadDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK.
Miguel Larraz Lopez De NovalesCambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
Cristian BulgaruCambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
Rafael KollyfasCambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
Julia WhittenEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Cory M WillisDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK.
Luka CuligEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Joseph LlewellynEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Rosana-Bristena IonescuDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK.
Magdy MekdadDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK.
Madalena B C Simões-AbadeDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK.
Grzegorz KrzakDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK.
Jinshui FanComputational Biology and Genomics Core, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Supriyo DeComputational Biology and Genomics Core, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Matthew O EllisDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK; UK Dementia Research Institute at University of Cambridge, Cambridge, UK.
Marta Suarez CuberoInstitute of Molecular Biology, Department of Genomics, Stem Cell Biology and Regenerative Medicine & CMBI, Leopold-Franzens-University Innsbruck, Innsbruck, Austria.
Angeliki SpathopoulouInstitute of Molecular Biology, Department of Genomics, Stem Cell Biology and Regenerative Medicine & CMBI, Leopold-Franzens-University Innsbruck, Innsbruck, Austria.
Luca Peruzzotti-JamettiDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK; Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK.
Tommaso LeonardiCenter for Genomic Science of IIT@SEMM, Instituto Italiano di Tecnologia (IIT), 20139 Milan, Italy.
Gabriel BalmusDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK; UK Dementia Research Institute at University of Cambridge, Cambridge, UK; Department of Molecular Neuroscience, Transylvanian Institute of Neuroscience, Cluj-Napoca, Romania.
Frank EdenhoferInstitute of Molecular Biology, Department of Genomics, Stem Cell Biology and Regenerative Medicine & CMBI, Leopold-Franzens-University Innsbruck, Innsbruck, Austria.
Myriam GorospeComputational Biology and Genomics Core, Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Lukas ValihrachLaboratory of Glial Biology and Omics Technologies, Institute of Biotechnology of the Czech Academy of Sciences, 25250 Vestec, Czech Republic.
Irina MohorianuCambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: iim22@cam.ac.uk.
Stefano PluchinoDepartment of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge CB2 0AH, UK. Electronic address: spp24@cam.ac.uk.
Isabel BeermanEpigenetics and Stem Cell Unit, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Electronic address: isabel.beerman@nih.gov.

Funding

Intramural NIH HHS Z99 AG999999Wellcome Trust
6 · The paper itself

Abstract

Progressive multiple sclerosis (PMS) involves a persistent, maladaptive inflammatory process with numerous cellular drivers. We generated induced neural stem cells (iNSCs) from patient fibroblasts through a direct reprogramming protocol that preserved their epigenome, which revealed a PMS-specific hypomethylation of lipid metabolism and interferon (IFN) signaling genes. Single-cell multi-omics uncovered a novel, disease-associated radial glia-like cell (DARG) subpopulation in PMS cell lines exhibiting senescence and potent IFN responsiveness driven by specific transcription factors. Functionally, PMS iNSCs induced paracrine senescence and inflammation onto control cells, which was inhibited upon senolytic treatment. We identified in PMS brains a distinct population of senescent, IFN-responsive DARGs that developmentally aligned with the trajectories of iNSCs in vitro and spatially associated with inflammatory glia in chronically active lesions. DARGs may sustain smoldering inflammation, unveiling a previously unrecognized cellular axis that could underpin mechanisms in neurodegeneration. This discovery offers novel insights into disease mechanisms and highlights potential therapeutic targets.

Indexed as

Ependymoglial CellsEpigenesis, GeneticInterferonsMultiple SclerosisMultiple Sclerosis, Chronic ProgressiveNeural Stem CellsCellular SenescenceHumansInterferonscellular senescenceepigenetic dysregulationinterferon responseneural stem cellsneurodegenerationprogressive multiple sclerosisradial glia-like cellssingle-cell multi-omicsspatial transcriptomicstranscriptomic signatures

Identifiers

PMID41075785
PMCPMC12834227

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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.