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Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation.

ABSTRACT: Engagement of the T cell receptor (TCR) triggers molecular reprogramming leading to the acquisition of specialized effector functions by CD4 helper and CD8 cytotoxic T cells. While transcription factors, chemokines, and cytokines are known drivers in this process, the temporal proteomic and transcriptomic changes that regulate different stages of human primary T cell activation remain to be elucidated. Here, we report an integrative temporal proteomic and transcriptomic analysis of primary human CD4 and CD8 T cells following ex vivo stimulation with anti-CD3/CD28 beads, which revealed major transcriptome-proteome uncoupling. The early activation phase in both CD4 and CD8 T cells was associated with transient downregulation of the mRNA transcripts and protein of the central glucose transport GLUT1. In the proliferation phase, CD4 and CD8 T cells became transcriptionally more divergent while their proteome became more similar. In addition to the kinetics of proteome-transcriptome correlation, this study unveils selective transcriptional and translational metabolic reprogramming governing CD4 and CD8 T cell responses to TCR stimulation. This temporal transcriptome/proteome map of human T cell activation provides a reference map exploitable for future discovery of biomarkers and candidates targeting T cell responses.

SUBMITTER: Weerakoon H

PROVIDER: S-EPMC10901835 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation.

Weerakoon Harshi H Mohamed Ahmed A Wong Yide Y Chen Jinjin J Senadheera Bhagya B Haigh Oscar O Watkins Thomas S TS Kazakoff Stephen S Mukhopadhyay Pamela P Mulvenna Jason J Miles John J JJ Hill Michelle M MM Lepletier Ailin A

NPJ systems biology and applications 20240228 1

Engagement of the T cell receptor (TCR) triggers molecular reprogramming leading to the acquisition of specialized effector functions by CD4 helper and CD8 cytotoxic T cells. While transcription factors, chemokines, and cytokines are known drivers in this process, the temporal proteomic and transcriptomic changes that regulate different stages of human primary T cell activation remain to be elucidated. Here, we report an integrative temporal proteomic and transcriptomic analysis of primary human ...[more]

PMID: 38418561

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Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation.

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Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation.

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