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

N -methyladenosine (m A) 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 m A sites within the individual cell types that make up the brain has not been possible. Here, we dev...

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Bibliographic Details
Published in:Nature neuroscience 2024-12, Vol.27 (12), p.2512
Main Authors: Tegowski, Matthew, Prater, Anna K, Holley, Christopher L, Meyer, Kate D
Format: Article
Language:English
Subjects:
Adenosine - analogs & derivatives
Adenosine - metabolism
Aging - genetics
Aging - metabolism
Animals
Brain - cytology
Brain - metabolism
Male
Methylation
Mice
Mice, Inbred C57BL
Neurons - metabolism
RNA, Messenger - metabolism
Single-Cell Analysis
Transcriptome
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Summary:N -methyladenosine (m A) 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 m A 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 m A detection in any tissue of interest at single-cell resolution. We use these mice to map m A 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 m A than other cell types. Finally, we perform single-cell m A mapping in aged mice and identify many transcripts with age-dependent changes in m A.
ISSN:1546-1726