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

Weerakoon, H; Mohamed, A; Wong, Y; Chen, J; Senadheera, B; Haigh, O; Watkins, TS; Kazakoff, S; Mukhopadhyay, P; Mulvenna, J; Miles, JJ; Hill, MM; Lepletier, A

Author(s): Weerakoon, H; Mohamed, A; Wong, Y; Chen, J; Senadheera, B; Haigh, O; Watkins, TS; Kazakoff, S; Mukhopadhyay, P; Mulvenna, J; Miles, JJ; Hill, MM; Lepletier, A;
Details: Publication Year 2024-02-28,Volume 10,Issue #1,Page 21
Journal Title: NPJ Systems Biology and Applications
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.
Publisher: Springer Nature
Keywords: Humans; *Proteome/genetics; CD3 Complex; *Transcriptome/genetics; Multiomics; Proteomics; Receptors, Antigen, T-Cell/genetics/metabolism
Research Division(s): Bioinformatics
PubMed ID: 38418561
Publisher's Version: https://doi.org/10.1038/s41540-024-00346-4
Open Access at Publisher's Site: https://doi.org/10.1038/s41540-024-00346-4
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-05-08 10:06:46

Last Modified: 2024-05-08 10:47:25