Murine single-cell RNA-seq reveals cell-identity- and tissue-specific trajectories of aging

被引:107
作者
Kimmel, Jacob C. [1 ]
Penland, Lolita [1 ]
Rubinstein, Nimrod D. [1 ]
Hendrickson, David G. [1 ]
Kelley, David R. [1 ]
Rosenthal, Adam Z. [1 ,2 ]
机构
[1] Calico Life Sci, San Francisco, CA 94080 USA
[2] DuPont Nutr & Biosci, Wilmington, DE 19803 USA
关键词
MUSCLE STEM-CELLS; GENE-EXPRESSION; FUNCTIONAL DECLINE; T-CELLS; MICE; TRANSCRIPTOME; DISCOVERY; RESPONSES; HETEROGENEITY; QUIESCENCE;
D O I
10.1101/gr.253880.119
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2088 / 2103
页数:16
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