Murine single-cell RNA-seq reveals cell-identity- and tissue-specific trajectories of aging
- Jacob C. Kimmel1,
- Lolita Penland1,2,
- Nimrod D. Rubinstein1,2,
- David G. Hendrickson1,
- David R. Kelley1 and
- Adam Z. Rosenthal1,3
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↵2 These authors contributed equally to this work.
Abstract
Aging is a pleiotropic process affecting many aspects of mammalian physiology. Mammals are composed of distinct cell type identities and tissue environments, but the influence of these cell identities and environments on the trajectory of aging in individual cells remains unclear. Here, we performed single-cell RNA-seq on >50,000 individual cells across three tissues in young and old mice to allow for direct comparison of aging phenotypes across cell types. We found transcriptional features of aging common across many cell types, as well as features of aging unique to each type. Leveraging matrix factorization and optimal transport methods, we found that both cell identities and tissue environments exert influence on the trajectory and magnitude of aging, with cell identity influence predominating. These results suggest that aging manifests with unique directionality and magnitude across the diverse cell identities in mammals.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.253880.119.
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Freely available online through the Genome Research Open Access option.
- Received June 20, 2019.
- Accepted October 21, 2019.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
