Single-Cell Epigenomics Uncovers Heterochromatin Instability and Transcription Factor Dysfunction during Mouse Brain Aging [snATAC-Seq] [10X Multiome]

We performed single-nucleus ATAC-seq (snATAC-seq) to profile chromatin accessibility across eight brain regions from C57BL/6J male and female mice at 2, 9, and 18 months of age. Nuclei were isolated from frozen dissected brain regions, tagmented using barcoded Tn5, and sequenced using combinatorial barcoding or 10x Multiome (female samples). Our analysis reveals region- and age-dependent chromatin changes, highlighting regulatory programs associated with aging in specific brain cell types. Single-nucleus ATAC-seq was performed on eight dissected brain regions (AMY, CP, ENT, RLP, NAC, AHC, PHC, FC) from male and female C57BL/6J mice at 2, 9, and 18 months of age. Male samples were processed using combinatorial indexing snATAC-seq; female samples were profiled using the 10x Genomics Single Cell Multiome ATAC + Gene Expression kit. For each brain region and age, 2–3 biological replicates consisting of pooled nuclei from 3–14 mice were used. Please note that the sample extract protocol has been updated on May 21, 2025. *************************************************************** The table below lists GEO accessions reused/reanalyzed for this study. ***************************************************************