@article{5e2954c831c340adb7f00fa367007cbf,
title = "Heterogeneity and transcriptome changes of human CD8+ T cells across nine decades of life",
abstract = "The decline of CD8+ T cell functions contributes to deteriorating health with aging, but the mechanisms that underlie this phenomenon are not well understood. We use single-cell RNA sequencing with both cross-sectional and longitudinal samples to assess how human CD8+ T cell heterogeneity and transcriptomes change over nine decades of life. Eleven subpopulations of CD8+ T cells and their dynamic changes with age are identified. Age-related changes in gene expression result from changes in the percentage of cells expressing a given transcript, quantitative changes in the transcript level, or a combination of these two. We develop a machine learning model capable of predicting the age of individual cells based on their transcriptomic features, which are closely associated with their differentiation and mutation burden. Finally, we validate this model in two separate contexts of CD8+ T cell aging: HIV infection and CAR T cell expansion in vivo.",
author = "Jian Lu and Raheel Ahmad and Thomas Nguyen and Jeffrey Cifello and Humza Hemani and Jiangyuan Li and Jinguo Chen and Siyi Li and Jing Wang and Achouak Achour and Joseph Chen and Meagan Colie and Ana Lustig and Christopher Dunn and Linda Zukley and Chia, {Chee W.} and Irina Burd and Jun Zhu and Luigi Ferrucci and Weng, {Nan ping}",
note = "Funding Information: Open Access funding provided by the National Institutes of Health (NIH). Funding Information: We thank Richard Hodes and Jiang Peng for critical reading and comments on the manuscript, Kimberly Jones-Beatty, and Mia Feller for helping collecting cord blood samples, and Christopher Dunn, Cuong Nguyen and Tonya Wolf for assistance with flow analysis and cell sorting. This work used the computational resources of the NIH HPC Biowulf cluster and was supported by the Intramural Research Programs of the National Institutes of Health National Institute on Aging and National Heart, Lung, and Blood Institute. Publisher Copyright: {\textcopyright} 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-32869-x",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}