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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
E-mail(s) peter.mcguire@nih.gov, payal.banerjee@nih.gov
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
Relations
BioProject PRJNA966911

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

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

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