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Series GSE172047 Query DataSets for GSE172047
Status Public on Mar 31, 2022
Title Control of regulatory T cell function by the non-oxidative pentose phosphate pathway [ATAC-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Non-oxidative pentose phosphate pathway (PPP) is a crucial gatekeeper of glucose catabolism in metabolic tissues. However, its role in regulatory T cells (Tregs) remains unknown. Here we report deleting transketolase (TKT), an indispensable enzyme of non-oxidative PPP, in Tregs caused a fatal auto-immune disease in mice. TKT deletion impaired suppressive capability without disturbing Treg cell number. Mechanistically, TKT deficiency caused Treg metabolic remodeling with decreased glucose catabolism, activated fatty acid and amino acid catabolism and uncontrolled oxidative phosphorylation. Moreover, excessive ammonia from deregulated amino acid catabolism impaired mitochondrial fitness while reduced α-ketoglutarate/succinate ratio led to DNA hypermethylation, limiting functional gene expression and suppressive activity of TKT-deficient Tregs. Therefore, our study identifies non-oxidative PPP as a new pathway for controlling Treg function.
 
Overall design 50,000 CD4+CD25+YFP+ Tregs were isolated from 7-week-old chimeric female WT and cKO mice by FACS and washed once with 50 μl cold PBS buffer. Supernatant was discarded by centrifugation at 500 g, 4oC for 5 min. Lysed the cell pellet in 50 μl cold lysis buffer (10 mM NaCl, 10 mM pH7.4 Tris-HCl; 0.5%NP-40 and 3mM MgCl2) and centrifuge immediately at 500g, 4°C for 10 min. Transposition reaction and purification PCR amplification were performed using Nextera XT DNA Library Preparation Kit (Illumina, Cat. #FC-131-1096) and Qiagen MinElute PCR Purification Kit (Qiagen, Cat. #28004). Illumina Novaseq 6000 was used for sequencing.
 
Contributor(s) Liu Q, Tong X
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Submission date Apr 14, 2021
Last update date Apr 02, 2022
Contact name Qi Liu
E-mail(s) liuqi0325@sjtu.edu.cn
Phone 13262626838
Organization name Shanghai Jiao Tong University School of Medicine
Street address 280 S. Chongqing Road
City shang hai
ZIP/Postal code 200025
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM5240631 WT1-Treg cells (ATAC-seq)
GSM5240632 cKO1-Treg cells (ATAC-seq)
This SubSeries is part of SuperSeries:
GSE172048 Control of regulatory T cell function by the non-oxidative pentose phosphate pathway
Relations
BioProject PRJNA721882
SRA SRP314801

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

Supplementary file Size Download File type/resource
GSE172047_RAW.tar 2.6 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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