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SRX4740144: GSM3400956: RNAseq_RISP_Chimera_WT4; Mus musculus; RNA-Seq
1 ILLUMINA (NextSeq 500) run: 44.3M spots, 3.3G bases, 1.4Gb downloads

Submitted by: NCBI (GEO)
Study: Mitochondrial complex III is essential for regulatory T cell suppressive function. [gene expression/RNA-seq]
show Abstracthide Abstract
Regulatory T cells (Treg cells), a distinct subset of CD4+ T cells, are necessary for the maintenance of immune self-tolerance and homeostasis. Recent studies have demonstrated that Treg cells display a unique metabolic profile characterized by an increase in mitochondrial metabolism relative to other CD4+ effector subsets. Furthermore, the Treg cell lineage-defining transcription factor, Foxp3, has been shown to promote respiration; however, it remains unknown whether the mitochondrial respiratory chain is required for Treg cell suppressive capacity, stability, and survival. Here we report that Treg cell-specific ablation of mitochondrial respiratory chain complex III results in the development of a fatal inflammatory disease early in life, without impacting Treg cell number. Mice lacking complex III specifically in Treg cells displayed a loss of Treg cell suppressive capacity without altering Treg cell proliferation and survival. Treg cells deficient in complex III display decreased expression of genes associated with Treg function while maintaining stable FOXP3 expression. Complex III-null Treg cells displayed increased DNA methylation at the loci of differentially down-regulated genes without a global increase in DNA methylation. Loss of complex III in Treg cells resulted in buildup of the metabolites 2-hydroxyglutarate (2-HG) and succinate that can function as inhibitors of a-ketoglutarate (a-KG)-dependent dioxygenase reactions such as the ten-eleven translocation (TET) family of DNA demethylases. Thus, Treg cells require mitochondrial respiration to maintain immune regulatory gene expression and suppressive function. Overall design: Each experiment contains either WT controls animals compared to KO animals, or untreated controls compared to treated conditions.
Sample: RNAseq_RISP_Chimera_WT4
SAMN10127802 • SRS3821607 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: NextSeq 500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: SINGLE
Construction protocol: NEB kit Cells were lysed with RLT Buffer from the Qiagen RNeasy Plus Mini kit (Qiagen). Cell lysates were stored at -80°C until RNA was extracted. RNA isolations were performed using Qiagen RNeasy Plus Micro/Mini kit (Qiagen) (Extended Data Fig. 5) or the AllPrep DNA/RNA Micro Kit (Qiagen) (Figure 3 and 4) following the manufacturer's protocol with an additional on-column DNase treatment using the RNase-Free DNase Set (Qiagen). RNA quality and quantity were measured using Agilent 4200 Tapestation using the high-sensitivity RNA ScreenTape System. (Agilent Technologies). mRNA libraries were prepared using the SMART-Seq v4 Ultra Low Input RNA Kit (Takara Bio USA, Inc) +Nextera XT DNA sample preparation kit (Illumina Inc) (Extended Data Fig. 5) or the NEBNext Ultra I RNA Library Prep Kit for Illumina with poly (A) mRNA selection (NEB Inc) (Figure 3,4).
Experiment attributes:
GEO Accession: GSM3400956
Links:
Runs: 1 run, 44.3M spots, 3.3G bases, 1.4Gb
Run# of Spots# of BasesSizePublished
SRR790367044,253,8143.3G1.4Gb2018-12-18

ID:
6422728

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