Trimodal single-cell profiling reveals a novel pediatric CD8αα+ T cell subset and broad age-related molecular reprogramming across the T cell compartment

Author:

Thomson Zachary,He ZiyuanORCID,Swanson ElliottORCID,Henderson Katherine,Phalen ColeORCID,Zaim Samir Rachid,Pebworth Mark-Phillip,Okada Lauren Y.ORCID,Heubeck Alexander T.ORCID,Roll Charles R.,Hernandez Veronica,Weiss Morgan,Genge Palak C.,Reading JulianORCID,Giles Josephine R.,Manne Sasikanth,Dougherty Jeanette,Jasen C. J.,Greenplate Allison R.ORCID,Becker Lynne A.ORCID,Graybuck Lucas T.ORCID,Vasaikar Suhas V.,Szeto Gregory L.,Savage Adam K.ORCID,Speake CateORCID,Buckner Jane H.ORCID,Li Xiao-junORCID,Bumol Thomas F.,Wherry E.JohnORCID,Torgerson Troy R.ORCID,Vella Laura A.,Henrickson Sarah E.,Skene Peter J.ORCID,Gustafson Claire E.ORCID

Abstract

AbstractAge-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.

Publisher

Springer Science and Business Media LLC

Subject

Immunology,Immunology and Allergy

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Cell fate decision in erythropoiesis: Insights from multiomics studies;Experimental Hematology;2024-01

2. Early innate role for CD8αα+ cells in tuberculosis;Journal of Experimental Medicine;2023-11-02

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3