A global view of aging and Alzheimer's pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains.

TitleA global view of aging and Alzheimer's pathogenesis-associated cell population dynamics and molecular signatures in human and mouse brains.
Publication TypeJournal Article
Year of Publication2023
AuthorsSziraki A, Lu Z, Lee J, Banyai G, Anderson S, Abdulraouf A, Metzner E, Liao A, Banfelder J, Epstein A, Schaefer C, Xu Z, Zhang Z, Gan L, Nelson PT, Zhou W, Cao J
JournalNat Genet
Volume55
Issue12
Pagination2104-2116
Date Published2023 Dec
ISSN1546-1718
KeywordsAging, Alzheimer Disease, Animals, Brain, Gene Expression Profiling, Humans, Mammals, Mice, Transcriptome
Abstract

Conventional methods fall short in unraveling the dynamics of rare cell types related to aging and diseases. Here we introduce EasySci, an advanced single-cell combinatorial indexing strategy for exploring age-dependent cellular dynamics in the mammalian brain. Profiling approximately 1.5 million single-cell transcriptomes and 400,000 chromatin accessibility profiles across diverse mouse brains, we identified over 300 cell subtypes, uncovering their molecular characteristics and spatial locations. This comprehensive view elucidates rare cell types expanded or depleted upon aging. We also investigated cell-type-specific responses to genetic alterations linked to Alzheimer's disease, identifying associated rare cell types. Additionally, by profiling 118,240 human brain single-cell transcriptomes, we discerned cell- and region-specific transcriptomic changes tied to Alzheimer's pathogenesis. In conclusion, this research offers a valuable resource for probing cell-type-specific dynamics in both normal and pathological aging.

DOI10.1038/s41588-023-01572-y
Alternate JournalNat Genet
PubMed ID38036784
PubMed Central IDPMC10703679
Grant ListP30 AG072946 / AG / NIA NIH HHS / United States
P01 AG078116 / AG / NIA NIH HHS / United States
RM1 HG011014 / HG / NHGRI NIH HHS / United States
R01 AG072758 / AG / NIA NIH HHS / United States
DP2 HG012522 / HG / NHGRI NIH HHS / United States
R01 AG076932 / AG / NIA NIH HHS / United States

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