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

Andras Sziraki, Ziyu Lu, Jasper Lee, Gabor Banyai, Sonya Anderson, Abdulraouf Abdulraouf, Eli Metzner, Andrew Liao, Jason Banfelder, Alexander Epstein, Chloe Schaefer, Zihan Xu, Zehao Zhang, Li Gan, Peter T. Nelson, Wei Zhou, Junyue Cao

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2104-2116
Number of pages13
JournalNature Genetics
Volume55
Issue number12
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

ASJC Scopus subject areas

  • Genetics

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