Genetics

This post covers three papers that sit at different distances from an actual metabolite measurement in MS. Chen and colleagues combine human MS optic-chiasm transcriptomics (GSE100297), glutamate-treated primary-neuron RNA sequencing (GSE255041), R28 differential-expression summaries and a single-nucleus atlas of normal human optic nerve (GSE236566), finding redox and lipid-peroxidation programmes highest in myeloid cells and hexosamine/O-GlcNAc programmes with SLC7A11 in astrocytic-stromal compartments, then test glucosamine and selenium in R28 cells: glucosamine at 2.5 mM shifts the glutamate dose-response rightward and preserves GSH/GSSG and respiration while lowering basal metabolic activity, membrane potential and ATP-based viability and raising O-GlcNAc 3.6-fold, selenium acts by dose with 20 microM raising basal lipid oxidation, glucosamine fails against RSL3 and erastin where ferrostatin-1 works, and the authors state the GPX4 dependence remains unresolved. Ahuja and colleagues build human myelin spheres from hPSC-derived neurons and oligodendrocyte precursors, run lipidomics and single-nuclei transcriptomics on the same cultures, see myelination by six weeks and maturation into compacted multilamellar sheaths resembling late fetal oligodendrocytes, and challenge the system with lysolecithin and Rabies virus. Jiang and colleagues infer lipid metabolism from transcriptional programmes alone in experimental autoimmune encephalomyelitis, describing Ki67, Acvrl1 and CD300ld-defined neutrophil subsets and a lung microenvironment that pushes CD300ld neutrophils toward immunosuppression, with analogous subsets in patients with MS.