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Aging activates, represses, and remodels the silent X chromosome and its escape across cell types of the female mouse hippocampus

GSE276652 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/11/05 Platform GPL24247
Summary
Females show an advantage in lifespan and cognition in aging human populations. The X chromosome is a major source of sex difference, as female mammals harbor an inactive (Xi) and active (Xa) following X chromosome inactivation (XCI). Whether Xi – or the silent X – can activate in the aging brain and thus increase X dose is unknown. Here, we performed single nuclei RNA-sequencing in the young and aging hippocampus of female mice and applied allele-specific computational analysis. We show that aging remodels transcription of Xi and Xa across hippocampal cell types. Aging preferentially induced gene expression changes on the X chromosomes compared to the autosomes. Xi underwent activation and repression of select genes, particularly in dentate gyrus neurons, critical to learning and memory.
Published in
Aging activates escape of the silent X chromosome in the female mouse hippocampus
Gadek M, Shaw CK, Abdulai-Saiku S et al. · Science advances 2025 · PMID 40043106 · doi:10.1126/sciadv.ads8169
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Also filed as BioProject PRJNA1158455 and SRA study SRP531367. Searching any of these in the dataset finder brings you back here.

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