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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 07, 2023 |
| Title |
Pyruvate dehydrogenase complex integrates the metabolome and epigenome in memory CD8+ T cell differentiation in vitro [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Modulation of metabolic flux through pyruvate dehydrogenase complex (PDC) plays an important role in T cell activation and differentiation. PDC sits at the transition between glycolysis and the tricarboxylic acid cycle and is a major producer of acetyl-CoA, marking it as a potential metabolic and epigenetic node. To understand the role of pyruvate dehydrogenase complex in T cell differentiation, we generated mice deficient in T cell pyruvate dehydrogenase E1A (Pdha) subunit using a CD4-cre recombinase-based strategy. Herein, we show that genetic ablation of PDC activity in T cells (TPdh-/-) leads to marked perturbations in glycolysis, the tricarboxylic acid cycle, and OXPHOS. Due to depressed OXPHOS, TPdh-/- T cells became dependent upon substrate level phosphorylation via glycolysis. Due to the block of PDC activity, histone acetylation was reduced, including H3K27, a critical site for CD8+ T cell memory differentiation. Transcriptional and functional profiling revealed abnormal CD8+ memory T cell differentiation in vitro. Collectively, our data indicate that PDC integrates the metabolome and epigenome in memory T cell differentiation. Targeting this metabolic and epigenetic node can have widespread ramifications on cellular function.
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| Overall design |
RNA-Seq
contributor: NISC Comparative Sequencing Program
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| Contributor(s) |
Tarasenko TN, Banerjee P, Gomez-Rodriguez J, Gildea DE, Zhang S, Wolfsberg TG, Jenkins L, McGuire PJ |
| Citation(s) |
37215014 |
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| Submission date |
May 03, 2023 |
| Last update date |
Aug 08, 2023 |
| Contact name |
Peter McGuire |
| E-mail(s) |
peter.mcguire@nih.gov, payal.banerjee@nih.gov
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| Organization name |
NHGRI
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| Street address |
10 Center Dr
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
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| GSM7290692 |
HHV57DSXY_19005456_S48,TT5_A,PDH_EFFECTOR |
| GSM7290693 |
HHV57DSXY_19005458_S52,TT6_A,PDH_EFFECTOR |
| GSM7290694 |
HHV57DSXY_19005460_S53,TT7_A,PDH_EFFECTOR |
| GSM7290695 |
HHV57DSXY_19005462_S61,TT8_A,PDH_EFFECTOR |
| GSM7290696 |
HHV57DSXY_19005464_S57,TT9_A,WT_MEMORY |
| GSM7290697 |
HHV57DSXY_19005466_S70,TT10_A,WT_MEMORY |
| GSM7290698 |
HHV57DSXY_19005468_S45,TT11_A,WT_MEMORY |
| GSM7290699 |
HHV57DSXY_19005470_S47,TT12_A,WT_MEMORY |
| GSM7290700 |
HHV57DSXY_19005472_S50,TT13_A,PDH_MEMORY |
| GSM7290701 |
HHV57DSXY_19005474_S56,TT14_A,PDH_MEMORY |
| GSM7290702 |
HHV57DSXY_19005476_S68,TT15_A,PDH_MEMORY |
| GSM7290703 |
HHV57DSXY_19005478_S46,TT16_A,PDH_MEMORY |
| GSM7290704 |
HHV57DSXY_19005480_S55,TT2_A,WT_EFFECTOR |
| GSM7290705 |
HHV57DSXY_19005482_S54,TT3_A,WT_EFFECTOR |
| GSM7290706 |
HHV57DSXY_19005484_S64,TT4_A,WT_EFFECTOR |
| GSM7290707 |
HHV57DSXY_19005496_S43,TT1_A,WT_EFFECTOR |
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| This SubSeries is part of SuperSeries: |
| GSE231556 |
Pyruvate dehydrogenase complex integrates the metabolome and epigenome in memory CD8+ T cell differentiation in vitro |
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| Relations |
| BioProject |
PRJNA966911 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE231553_RAW.tar |
18.1 Mb |
(http)(custom) |
TAR (of RESULTS) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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