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

Sziraki, Andras, Lu, Ziyu, Lee, Jasper, Banyai, Gabor, Anderson, Sonya, Abdulraouf, Abdulraouf, Metzner, Eli, Liao, Andrew +9 more·2023·Nature Genetics
DOI 10.1038/s41588-023-01572-yPMC PMC10703679

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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.

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  • A comprehensive molecular characterization of region-specific differences in Alzheimer's disease is currently lacking.

    “Although some brain regions relevant to AD have been studied individually at scale or jointly in samples from a few individuals8–16, a comprehensive molecular characterization of region-specific differences in AD is currently lacking”

    From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [16]

    The Main section says prior studies sampled brain cell populations relatively shallowly, supporting a general gap in comprehensive characterization. The Results section identifies region-specific AD gene signatures in two human brain regions, but the paper does not explicitly say that a comprehensive molecular characterization of region-specific differences in AD is currently lacking. No page numbers are available in our copy. (LLM, conf=0.77)

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Cited by

Sorted by citations

Authors
Sziraki, 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, P. T., Zhou, W., & Cao, J.
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2023-11-30
Volume
55
Issue
12
Pages
2104-2116
ISSN
  • 1061-4036
  • 1546-1718
DOI
10.1038/s41588-023-01572-y
PMC
PMC10703679
Cited by
100
References
23
Language
en
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