Characterizing the mechanisms of somatic mutations in the brain is important for understanding aging and disease, but little is known about the mutational patterns of different cell types. We performed whole-genome sequencing of 86 single oligodendrocytes, 20 mixed glia, and 56 single neurons from neurotypical individuals (0.4 to 104 years old) and compared the rates and signatures of somatic single nucleotide variants (sSNVs) and small insertions and deletions (indels) from each cell type. We further correlated this data with single-cell RNA (scRNA-seq) and chromatin accessibility (scATAC-seq) data generated from the same brains to compare the mutagenic processes in glia and neurons.

Christopher A. Walsh, MD, PhD
Boston Children’s Hospital


Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

For investigators using Rates and mechanisms of age-related somatic mutation in normal and Alzheimer brain data:

Sequencing data from this study was generated with support from the National Institute on Aging (R01AG070921) to Christopher A. Walsh at Boston Children’s Hospital.

Ganz J, Luquette LJ, et al. Contrasting somatic mutation patterns in aging human neurons and oligodendrocytes. Cell. 2024 Apr. doi: 10.1016/j.cell.2024.02.025. PubMed link