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Single-cell m6A profiling in the mouse brain uncovers cell type-specific RNA methylomes and age-dependent differential methylation

GSE266876 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/09/24 Platform GPL24247
Summary
N6-methyladenosine (m6A) is an abundant mRNA modification in the brain which plays important roles in neurodevelopment and brain function. However, due to technical limitations, global profiling of m6A sites within the individual cell types that make up the brain has not been possible. Here, we develop a mouse model that enables transcriptome-wide m6A detection in any tissue of interest and at single-cell resolution. We use these mice to map m6A across different brain regions and within single cells of the mouse cortex and discover a high degree of shared methylation across brain regions and cell types. However, we also identify a small number of differentially methylated mRNAs in neurons that encode important regulators of neuronal signaling, and we discover that microglia have lower levels of m6A compared to other cell types. Finally, we perform single-cell m6A mapping in aged mice and identify many transcripts with age-dependent changes in m6A.
Published in
Single-cell m(6)A profiling in the mouse brain uncovers cell type-specific RNA methylomes and age-dependent differential methylation
Tegowski M, Prater AK, Holley CL et al. · Nature neuroscience 2024 · PMID 39317796 · doi:10.1038/s41593-024-01768-3
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Direct links to NCBI, no account and no request form: the whole study as GSE266876_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA996152 and SRA study SRP450587. Searching any of these in the dataset finder brings you back here.

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