GEO series

Temporal changes in metabolism guide oligodendrocyte precursor cell dynamics in aging and multiple sclerosis [BulkRNAseq]

GSE330029 Homo sapiens Expression profiling by high throughput sequencing 108 samples Submitted 2026/08/07 Platform GPL34284

Summary

Impaired oligodendrocyte precursor cell (OPC) differentiation limits myelin renewal in aging and contributes to multiple sclerosis (MS) progression. How aging drives OPC deficits remains incompletely understood. We find dysregulation of genes associated with the circadian clock, including Bmal1, and metabolism in aged compared with young OPCs. Targeted loss of Bmal1 in OPCs drives metabolic dysfunction, leading to cellular senescence and impaired dynamics. OPC proliferation and differentiation occur at different rates throughout the day in young adult mice and become disrupted with aging. Chronotherapeutic targeting of BMAL1-controlled sirtuin signaling restores Bmal1-disrupted OPC dynamics after demyelination via sirtuin 2 (Sirt2)-dependent mechanisms. Induced pluripotent stem cell (iPSC)-derived OPCs from MS patients and MS lesion oligodendroglia recapitulate BMAL1 and SIRT2 disruptions. These findings establish BMAL1 as a key regulator of OPC energy metabolism, sirtuin homeostasis, and senescence. We anticipate that this work will provide a foundation for future studies investigating the interconnected roles of aging, circadian disruption, and myelin biology.

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Direct links to NCBI, no account and no request form: the whole study as GSE330029_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 108 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1462594 and SRA study SRP697879. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

13 conditions, mostly in triplicate

iPSC-derived OPCs, control_2, CT24, differtia… ×3 iPSC-derived OPCs, control_3, CT24, differtia… ×3 iPSC-derived OPCs, RRMS_1, CT24, differtiation ×3 iPSC-derived OPCs, RRMS_3, CT24, differtiation ×3 iPSC-derived OPCs, SPMS_1, CT24, differtiation ×3 iPSC-derived OPCs, SPMS_2, CT24, differtiation ×3 iPSC-derived OPCs, SPMS_3, CT24, differtiation ×3 iPSC-derived OPCs, control_2, CT30, differtia… ×3 +9 more

Supports a between-group comparison across 36 samples.

13 replicated groups read from the first 40 of 108 sample titles; they account for 36 of them. Check it against the sample list below before relying on it.

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