Dataset Information

Single-nucleus transcriptomic sequencing and cross integration comparison of multiple species revealed new cell composition and specific gene marker in hippocampal aging

ABSTRACT: Brain aging is a major risk factor for many brain diseases, which seriously affects the quality of life and even life span, and poses an increasingly serious threat to human health. Research shows that anti-aging and an extra year of life expectancy could bring $38 trillion in economic gains. Therefore, it is urgent to study the mechanism of brain aging, find effective ways to improve aging and improve the quality of life of the aging population. In the early stage, we established the culture system of activated urine stem cells (aUSCs), which can significantly improve the nerve cell senescence in vitro and brain aging of natural aging mice and macaques, suggesting that aUSCs have strong anti-brain aging ability; The results of single-nucleus sequencing of mouse hippocampus suggested that anti-aging was achieved by changing the glial cell subset to constitutively inhibit inflammatory signaling to reduce inflammatory response. Based on this, this topic continues to conduct aUSCs intervention on naturally aging rhesus monkeys to study the anti-brain aging effect and potential mechanism of aUSCs in non-human primates; Meanwhile, the human cerebral organoid model was applied to further study the anti-brain aging effect and potential mechanism of aUSCs in the human brain. Therefore, this topic not only screens seed cells for state-supported stem cell transformation applications, but also provides solutions for the problems caused by world aging, which has great scientific significance and economic value. In order to explore the mechanism of aUSCs anti-brain aging, we used single-cell sequencing to analyze the effect of aUSCs on the hippocampus of aging mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE230451 | GEO | 2024/04/30

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:A detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism. The brain cortex and hippocampus of young and aged mice of wild-type and ApoD-KO genotypes were used for RNA extraction and hybridization on Affymetrix microarrays. We aim at identifying distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus.

Dataset Information

Single-nucleus transcriptomic sequencing and cross integration comparison of multiple species revealed new cell composition and specific gene marker in hippocampal aging

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure