ArticleThe Journal of clinical investigation2023
Deficiency in the omega-3 lysolipid transporter Mfsd2a leads to aberrant oligodendrocyte lineage development and hypomyelination.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Plasma lipidomic and metabolomic profiles in high-grade glioma patients before and after 72-h presurgery water-only fasting.Molecular oncology · 2025Trial
- Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2025Trial
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.Molecular biomedicine · 2026Review
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Mfsd2a is important for maintaining epidermal homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- MFSD2A: a molecular nexus linking blood-brain barrier, lipid metabolism, and ischemia-reperfusion injury.Cellular & molecular biology letters · 2025Review
- Maternal Inflammation During Pregnancy and Cord Blood Metabolomic Signatures in the Context of HIV Exposure.Metabolites · 2025Article
- The Serum Lipid Profile of Relapsing Multiple Sclerosis Differs Reproducibly From Healthy Controls.Journal of neurochemistry · 2025Article
- Machine learning-based prediction of disease progression in primary progressive multiple sclerosis.Brain communications · 2025Article
- Modified neuroimmune processes and emotional behaviour in weaned and late adolescent male and female mice born via caesarean section.Scientific reports · 2024Article
- Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with autosomal recessive microcephaly 15 caused by deficiency in the sodium-dependent lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain-containing 2a (Mfsd2a) present with both microcephaly and hypomyelination, suggesting an important role for LPC uptake by oligodendrocytes in the process of myelination. Here we demonstrate that Mfsd2a is specifically expressed in oligodendrocyte precursor cells (OPCs) and is critical for oligodendrocyte development. Single-cell sequencing of the oligodendrocyte lineage revealed that OPCs from OPC-specific Mfsd2a-KO mice (2aOKO mice) underwent precocious differentiation into immature oligodendrocytes and impaired maturation into myelinating oligodendrocytes, correlating with postnatal brain hypomyelination. 2aOKO mice did not exhibit microcephaly, a finding consistent with the notion that microcephaly is the consequence of an absence of LPC uptake at the blood-brain barrier rather than a deficiency in OPCs. Lipidomic analysis showed that OPCs and iOLs from 2aOKO mice had significantly decreased levels of phospholipids containing omega-3 fatty acids, with a corresponding increase in unsaturated fatty acids, the latter being products of de novo synthesis governed by Srebp-1. RNA-Seq indicated activation of the Srebp-1 pathway and defective expression of regulators of oligodendrocyte development. Taken together, these findings indicate that the transport of LPCs by Mfsd2a in OPCs is important for maintaining OPC state to regulate postnatal brain myelination.
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