{
  "abstract": "Pathogenic variants in MSL2, a core component of the histone-modifying MSL complex, are associated with neurodevelopmental disorders (NDDs) and white matter abnormalities; however, their mechanisms of pathogenicity remain unknown. In this study, we identified three patients with NDD carrying MSL2 variants, all of whom exhibited white matter abnormalities. Using conditional knockout mice, we demonstrated that oligodendrocyte lineage-specific deletion of Msl2 disrupts oligodendrocyte precursor cell proliferation, maturation, and myelination in a cell-autonomous manner, leading to autism-like behaviors including social deficits and repetitive behaviors. Integrated transcriptomic and epigenomic profiling revealed that MSL2 maintains H3K4me3 occupancy at promoters of genes essential for cell cycle progression, mitotic spindle assembly, and myelination, whereas its loss aberrantly activates immune-related pathways. Furthermore, a cell synchronization study confirmed that MSL2 is required for metaphase spindle formation in oligodendrocyte precursor cells, providing a mechanistic basis for impaired oligodendroglial development and hypomyelination. Our findings establish MSL2 as a critical epigenetic regulator of oligodendrocyte lineage progression and propose MSL2-targeted interventions as a promising therapeutic strategy for NDD-related white matter defects.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi’an, Shaanxi China",
    "The Shaanxi Province Key Laboratory of Brain Function Analysis and Modulation, Xi’an, Shaanxi China",
    "Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, Central South University, Changsha, Hunan China",
    "Department of Medical Genetics, The Affiliated Children’s Hospital of Xiangya School of Medicine (Hunan Children’s Hospital), Central South University, Changsha, Hunan China",
    "Genetica AG, Human Genetics and Genetic Counselling Unit, Zurich, Switzerland",
    "Hunter Genetics, Waratah, NSW Australia",
    "School of Medicine and Public Health, University of Newcastle, Callaghan, NSW Australia",
    "Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC Australia",
    "Department of Paediatrics, University of Melbourne, Melbourne, VIC Australia"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jie Yuan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuhao Dong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kaixiang Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhongcheng Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhongzhe Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ming Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Shengjie Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Sufang Jiang"
    },
    {
      "affs": [
        3
      ],
      "name": "Yu Peng"
    },
    {
      "affs": [
        3
      ],
      "name": "Xinghan Wu"
    },
    {
      "affs": [
        4
      ],
      "name": "Herenger Yvan"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Himanshu Goel"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Elaine Zhang"
    },
    {
      "name": "The Australian Undiagnosed Diseases Network (UDN-Aus)"
    },
    {
      "affs": [
        2
      ],
      "name": "Hui Guo",
      "orcid": "0000-0002-1570-2545"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shengxi Wu",
      "orcid": "0000-0002-3210-9567"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xianghui Zhao",
      "orcid": "0000-0003-1165-0140"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0cax4efpskvzg.bib",
  "cited_by": 0,
  "doi": "10.1038/s12276-026-01858-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736987/",
  "id": "0cax4efpskvzg",
  "issns": [
    "1226-3613",
    "2092-6413"
  ],
  "landing_url": "https://doi.org/10.1038/s12276-026-01858-1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
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  ],
  "openalex": "W7220728427",
  "pdf_url": "https://www.nature.com/articles/s12276-026-01858-1.pdf",
  "pmcid": "PMC13736987",
  "pmid": "42839016",
  "published": "2026-10-06",
  "publisher": "Korean Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/0cax4efpskvzg.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:18Z",
      "native_id": "PMC13736987",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s12276-026-01858-1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetics and Neurodevelopmental Disorders",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "MSL2 orchestrates oligodendrocyte precursor cell cycle via H3K4me3 to prevent white matter defects in neurodevelopmental disorders",
  "title_text": "MSL2 orchestrates oligodendrocyte precursor cell cycle via H3K4me3 to prevent white matter defects in neurodevelopmental disorders",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:18Z",
  "url": "https://research.draconitic.com/paper/0cax4efpskvzg",
  "venue": "Experimental & Molecular Medicine",
  "versions": []
}