Single-cell transcriptomic and genomic changes in the aging human brain.
Ailsa M JeffriesTianxiong YuJennifer S ZiegenfussAllie K TollesYerin KimZhiping WengMichael A LodatoPublished in: bioRxiv : the preprint server for biology (2023)
Aging 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.
Keyphrases
- single cell
- rna seq
- genome wide
- genome wide identification
- high throughput
- copy number
- dna repair
- bioinformatics analysis
- poor prognosis
- prefrontal cortex
- dna methylation
- dna damage
- gene expression
- stem cells
- induced apoptosis
- oxidative stress
- transcription factor
- physical activity
- white matter
- long non coding rna
- dna damage response
- blood brain barrier
- mesenchymal stem cells
- congenital heart disease
- cell cycle arrest
- bone marrow
- cell proliferation