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Heterogeneity and transcriptome changes of human CD8+ T cells across nine decades of life.

Jian Lu | Raheel Ahmad | Thomas Nguyen | Jeffrey Cifello | Humza Hemani | Jiangyuan Li | Jinguo Chen | Siyi Li | Jing Wang | Achouak Achour | Joseph Chen | Meagan Colie | Ana Lustig | Christopher Dunn | Linda Zukley | Chee W Chia | Irina Burd | Jun Zhu | Luigi Ferrucci | Nan-Ping Weng
Nature communications | 2022

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.

Pubmed ID: 36050300

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


GATK (tool)

RRID:SCR_001876

A software package to analyze next-generation resequencing data. The toolkit offers a wide variety of tools, with a primary focus on variant discovery and genotyping as well as strong emphasis on data quality assurance. Its robust architecture, powerful processing engine and high-performance computing features make it capable of taking on projects of any size. This software library makes writing efficient analysis tools using next-generation sequencing data very easy, and second it's a suite of tools for working with human medical resequencing projects such as 1000 Genomes and The Cancer Genome Atlas. These tools include things like a depth of coverage analyzers, a quality score recalibrator, a SNP/indel caller and a local realigner. (entry from Genetic Analysis Software)

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Gene Set Enrichment Analysis (tool)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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FlowJo (tool)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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GEMS (tool)

RRID:SCR_009188

THIS RESOURCE IS NO LONGER IN SERVCE, documented September 22, 2016. Software application for fitting Genetic Epidemiology Models by running stochastic simulation in relation to disease dynamics.

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BD Biosciences (tool)

RRID:SCR_013311

An Antibody supplier

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