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Publication : Single-cell m(6)A profiling in the mouse brain uncovers cell type-specific RNA methylomes and age-dependent differential methylation.

First Author  Tegowski M Year  2024
Journal  Nat Neurosci Volume  27
Issue  12 Pages  2512-2520
PubMed ID  39317796 Mgi Jnum  J:358650
Mgi Id  MGI:7783567 Doi  10.1038/s41593-024-01768-3
Citation  Tegowski M, et al. (2024) Single-cell m6A profiling in the mouse brain uncovers cell type-specific RNA methylomes and age-dependent differential methylation. 6A profiling in the mouse brain uncovers cell type-specific RNA methylomes and age-dependent differential methylation. Nat Neurosci
abstractText  N6-methyladenosine (m6A) is an abundant mRNA modification in the brain that has important roles in neurodevelopment and brain function. However, because of 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 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 than other cell types. Finally, we perform single-cell m6A mapping in aged mice and identify many transcripts with age-dependent changes in m6A.
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