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Series GSE231553 Query DataSets for GSE231553
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
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.
Overall design RNA-Seq
contributor: NISC Comparative Sequencing Program
Contributor(s) Tarasenko TN, Banerjee P, Gomez-Rodriguez J, Gildea DE, Zhang S, Wolfsberg TG, Jenkins L, McGuire PJ
Citation(s) 37215014
Submission date May 03, 2023
Last update date Aug 08, 2023
Contact name Peter McGuire
Organization name NHGRI
Street address 10 Center Dr
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (16)
GSM7290692 HHV57DSXY_19005456_S48,TT5_A,PDH_EFFECTOR
GSM7290693 HHV57DSXY_19005458_S52,TT6_A,PDH_EFFECTOR
GSM7290694 HHV57DSXY_19005460_S53,TT7_A,PDH_EFFECTOR
This SubSeries is part of SuperSeries:
GSE231556 Pyruvate dehydrogenase complex integrates the metabolome and epigenome in memory CD8+ T cell differentiation in vitro
BioProject PRJNA966911

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Supplementary file Size Download File type/resource
GSE231553_RAW.tar 18.1 Mb (http)(custom) TAR (of RESULTS)
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Raw data are available in SRA
Processed data provided as supplementary file

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