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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-024-00346-4 |
| _version_ | 1797274168034590720 |
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| author | Harshi Weerakoon Ahmed Mohamed Yide Wong Jinjin Chen Bhagya Senadheera Oscar Haigh Thomas S. Watkins Stephen Kazakoff Pamela Mukhopadhyay Jason Mulvenna John J. Miles Michelle M. Hill Ailin Lepletier |
| author_facet | Harshi Weerakoon Ahmed Mohamed Yide Wong Jinjin Chen Bhagya Senadheera Oscar Haigh Thomas S. Watkins Stephen Kazakoff Pamela Mukhopadhyay Jason Mulvenna John J. Miles Michelle M. Hill Ailin Lepletier |
| author_sort | Harshi Weerakoon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:55:30Z |
| format | Article |
| id | doaj.art-6c5f2dbb912e4bc28c94d62032105a3d |
| institution | Directory Open Access Journal |
| issn | 2056-7189 |
| language | English |
| last_indexed | 2024-03-07T14:55:30Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj.art-6c5f2dbb912e4bc28c94d62032105a3d2024-03-05T19:28:49ZengNature Portfolionpj Systems Biology and Applications2056-71892024-02-0110111310.1038/s41540-024-00346-4Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activationHarshi Weerakoon0Ahmed Mohamed1Yide Wong2Jinjin Chen3Bhagya Senadheera4Oscar Haigh5Thomas S. Watkins6Stephen Kazakoff7Pamela Mukhopadhyay8Jason Mulvenna9John J. Miles10Michelle M. Hill11Ailin Lepletier12QIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteBioinformatics Division, The Walter and Eliza Hall Institute of Medical ResearchSchool of Computing, University of ColomboQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteAbstract 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.https://doi.org/10.1038/s41540-024-00346-4 |
| spellingShingle | Harshi Weerakoon Ahmed Mohamed Yide Wong Jinjin Chen Bhagya Senadheera Oscar Haigh Thomas S. Watkins Stephen Kazakoff Pamela Mukhopadhyay Jason Mulvenna John J. Miles Michelle M. Hill Ailin Lepletier Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation npj Systems Biology and Applications |
| title | Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation |
| title_full | Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation |
| title_fullStr | Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation |
| title_full_unstemmed | Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation |
| title_short | Integrative temporal multi-omics reveals uncoupling of transcriptome and proteome during human T cell activation |
| title_sort | integrative temporal multi omics reveals uncoupling of transcriptome and proteome during human t cell activation |
| url | https://doi.org/10.1038/s41540-024-00346-4 |
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