GEO series
Metformin enhances human oligodendrocyte function by altering metabolism
GSE282369
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
17 samples
Submitted 2024/12/10
Platform GPL24676Platform GPL25526
Summary
Metformin rejuvenates adult rat oligodendrocyte progenitor cells (OPCs) allowing more efficient differentiation into oligodendrocytes and improved remyelination of CNS axons and therefore is of interest as a possible therapeutic in demyelinating diseases such as multiple sclerosis (MS). We set out to test whether metformin had a similar effect in human stem cell derived-OPCs. We assessed the suitability of human monoculture, organoid and transplantation into immunodeficient mice (chimera model) culture systems in simulating in vivo adult human oligodendrocytes, finding most close resemblance in the chimera model. Metformin increased myelin proteins and/or sheaths in all models even when human cells had fetal signatures. In the chimera model, metformin led to a marked increase in mitochondrial area both in the human transplanted cells and in the mouse axons with associated increase in transcripts related to mitochondrial function and metabolism. Human oligodendrocytes from MS brain donors treated pre-mortem with metformin also expressed similar transcripts suggesting that metformin’s brain effect is not cell-specific, altering metabolism in both oligodendrocytes and axons leading to more myelin production, in part through mitochondrial changes. This bodes well for ongoing clinical trials testing metformin for neuroprotection.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE282369_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 17 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1188459 and SRA study SRP546369. Searching any of these in the dataset finder brings you back here.
Study design
6 conditions, mostly in triplicate
cortical_organoid_oligodendroglia ×4
monolayer_oligodendroglia ×3
chimeric_oligodendroglia_MET ×3
chimeric_human_filtered_oligodendroglia_MET ×3
chimeric_oligodendroglia_CTRL ×2
chimeric_human_filtered_oligodendroglia_CTRL ×2
Supports a between-group comparison across 17 samples.
6 replicated groups read from 17 sample titles; they account for 17 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8642078 monolayer_oligodendroglia_1
- GSM8642079 monolayer_oligodendroglia_2
- GSM8642080 monolayer_oligodendroglia_3
- GSM8642081 cortical_organoid_oligodendroglia_1
- GSM8642082 cortical_organoid_oligodendroglia_2
- GSM8642083 cortical_organoid_oligodendroglia_3
- GSM8642084 cortical_organoid_oligodendroglia_4
- GSM8642085 chimeric_oligodendroglia_CTRL_1
- GSM8642086 chimeric_oligodendroglia_CTRL_2
- GSM8642087 chimeric_oligodendroglia_MET_1
- GSM8642088 chimeric_oligodendroglia_MET_2
- GSM8642089 chimeric_oligodendroglia_MET_3
- GSM8642090 chimeric_human_filtered_oligodendroglia_CTRL_1
- GSM8642091 chimeric_human_filtered_oligodendroglia_CTRL_2
- GSM8642092 chimeric_human_filtered_oligodendroglia_MET_1
- GSM8642093 chimeric_human_filtered_oligodendroglia_MET_2
- GSM8642094 chimeric_human_filtered_oligodendroglia_MET_3
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