Single-cell transcriptomic and genomic changes in the aging human brain [preprint]
AuthorsJeffries, Ailsa M
Ziegenfuss, Jennifer S
Tolles, Allie K
Lodato, Michael A
Student AuthorsAilsa M Jeffries
UMass Chan AffiliationsMolecular, Cell and Cancer Biology
Morningside Graduate School of Biomedical Sciences
Program in Bioinformatics and Integrative Biology
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AbstractAging brings dysregulation of various processes across organs and tissues, often stemming from stochastic damage to individual cells over time. Here, we used a combination of single-nucleus RNA-sequencing and single-cell whole-genome sequencing to identify transcriptomic and genomic changes in the prefrontal cortex of the human brain across life span, from infancy to centenarian. We identified infant-specific cell clusters enriched for the expression of neurodevelopmental genes, and a common down-regulation of cell-essential homeostatic genes that function in ribosomes, transport, and metabolism during aging across cell types. Conversely, expression of neuron-specific genes generally remains stable throughout life. We observed a decrease in specific DNA repair genes in aging, including genes implicated in generating brain somatic mutations as indicated by mutation signature analysis. Furthermore, we detected gene-length-specific somatic mutation rates that shape the transcriptomic landscape of the aged human brain. These findings elucidate critical aspects of human brain aging, shedding light on transcriptomic and genomics dynamics.
SourceJeffries AM, Yu T, Ziegenfuss JS, Tolles AK, Kim Y, Weng Z, Lodato MA. Single-cell transcriptomic and genomic changes in the aging human brain. bioRxiv [Preprint]. 2023 Nov 7:2023.11.07.566050. doi: 10.1101/2023.11.07.566050. PMID: 37986960; PMCID: PMC10659272.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52869
NotesThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
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