학술논문
Trimodal single-cell profiling reveals a novel pediatric CD8αα+ T cell subset and broad age-related molecular reprogramming across the T cell compartment
Document Type
Original Paper
Author
Thomson, Zachary; He, Ziyuan; Swanson, Elliott; Henderson, Katherine; Phalen, Cole; Zaim, Samir Rachid; Pebworth, Mark-Phillip; Okada, Lauren Y.; Heubeck, Alexander T.; Roll, Charles R.; Hernandez, Veronica; Weiss, Morgan; Genge, Palak C.; Reading, Julian; Giles, Josephine R.; Manne, Sasikanth; Dougherty, Jeanette; Jasen, C. J.; Greenplate, Allison R.; Becker, Lynne A.; Graybuck, Lucas T.; Vasaikar, Suhas V.; Szeto, Gregory L.; Savage, Adam K.; Speake, Cate; Buckner, Jane H.; Li, Xiao-jun; Bumol, Thomas F.; Wherry, E.John; Torgerson, Troy R.; Vella, Laura A.; Henrickson, Sarah E.; Skene, Peter J.; Gustafson, Claire E.
Source
Nature Immunology. 24(11):1947-1959
Subject
Language
English
ISSN
1529-2908
1529-2916
1529-2916
Abstract
Age-associated changes in the T cell compartment are well described. However, limitations of current single-modal or bimodal single-cell assays, including flow cytometry, RNA-seq (RNA sequencing) and CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), have restricted our ability to deconvolve more complex cellular and molecular changes. Here, we profile >300,000 single T cells from healthy children (aged 11–13 years) and older adults (aged 55–65 years) by using the trimodal assay TEA-seq (single-cell analysis of mRNA transcripts, surface protein epitopes and chromatin accessibility), which revealed that molecular programming of T cell subsets shifts toward a more activated basal state with age. Naive CD4+ T cells, considered relatively resistant to aging, exhibited pronounced transcriptional and epigenetic reprogramming. Moreover, we discovered a novel CD8αα+ T cell subset lost with age that is epigenetically poised for rapid effector responses and has distinct inhibitory, costimulatory and tissue-homing properties. Together, these data reveal new insights into age-associated changes in the T cell compartment that may contribute to differential immune responses.
Using TEA-seq, Thomson et al. detail transcriptional and epigenetic alterations in the T cell compartment between healthy children and older adults, leading to the discovery of a novel pediatric CD8αα+ population poised for rapid effector responses.
Using TEA-seq, Thomson et al. detail transcriptional and epigenetic alterations in the T cell compartment between healthy children and older adults, leading to the discovery of a novel pediatric CD8αα