ArticleActa neuropathologica communications2023
Localized microglia dysregulation impairs central nervous system myelination in development.
Article in Acta neuropathologica communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Oligodendrocyte dysfunction in human age-related cognitive decline.Nature medicine · 2026Article
- Osteopontin in the Central Nervous System: Roles in Development, Injury, Neurodegeneration, and Neuro-Oncology.Biomolecules · 2026Review
- ACSS2 maintains oligodendrocyte progenitor cell pool and is required for myelination during development and aging.Nature aging · 2026Article
- Oligodendrocyte dysfunction in neurodegenerative diseases: pathological features, underlying mechanisms and therapeutic targeting.Frontiers in aging neuroscience · 2026Review
- A systematic scoring system to optimise the testing of neurotherapeutics in models of perinatal brain injury, with an applied case study of human umbilical-cord MSC.Journal of neuroinflammation · 2025Article
- Evaluation of the Efficacy of a Full-Spectrum Low-THCBiomolecules · 2024Article
- Maternal obesity alters fetal neuroinflammation in a murine model of preterm birth.AJOG global reports · 2024Article
- The molecular determinants of microglial developmental dynamics.Nature reviews. Neuroscience · 2024Review
- Review
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Myelination of neuronal axons is a critical aspect of central nervous system development and function. However, the fundamental cellular and molecular mechanisms influencing human developmental myelination and its failure are not fully understood. Here, we used digital spatial transcriptomics of a rare bank of human developing white matter to uncover that a localized dysregulated innate immune response is associated with impeded myelination. We identified that poorly myelinating areas have a distinct signature of Type II interferon signalling in microglia/macrophages, relative to adjacent myelinating areas. This is associated with a surprising increase in mature oligodendrocytes, which fail to form myelin processes appropriately. We functionally link these findings by showing that conditioned media from interferon-stimulated microglia is sufficient to dysregulate myelin process formation by oligodendrocytes in culture. We identify the Type II interferon inducer, Osteopontin (SPP1), as being upregulated in poorly myelinating brains, indicating a potential biomarker. Our results reveal the importance of microglia-mature oligodendrocyte interaction and interferon signaling in regulating myelination of the developing human brain.
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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.