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Series GSE63794 Query DataSets for GSE63794
Status Public on Dec 03, 2014
Title Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary RNA sequencing of wild-type or Interferon Alpha receptor 1 Knockout MEF cells treated with DMSO or the Caspase Inhibitor Q-VD-OPh.

The mechanism by which cells undergo death determines whether dying cells trigger inflammatory responses or remain immunologically silent. Mitochondria play a central role in the induction of cell death, as well as in immune signaling pathways. Here, we identify of a mechanism by which mitochondria and downstream pro-apoptotic caspases regulate the activation of antiviral immunity. In the absence of active caspases, mitochondrial outer membrane permeabilization by Bax and Bak results in the expression of type I interferons (IFNs). This induction is mediated by mitochondrial DNA-dependent activation of the cGAS/STING pathway and results in the establishment of a potent state of viral resistance. Our results show that mitochondria have the capacity to simultaneously expose a cell-intrinsic inducer of the IFN response, and to inactivate this response in a caspase-dependent manner. This mechanism provides a dual control, which determines whether mitochondria initiate an immunologically silent or a pro-inflammatory type of cell death.

In order to determine whether the pharmacological inhibition of caspases could activate the type I interferon response, we treated WT MEFs with the caspase inhibitor Q-VD-OPH. The inhibitor induced an increased expression of ISGs, which was dependent on type I IFN receptor (IFNAR1) signaling.
Overall design RNA was extracted from duplicate samples and libraries generated for sequencing using the directional RNA-Seq library prep at the Yale Center for Genome Analysis. Libraries were sequenced using a Hiseq2500 sequencer to generate 76bp single-end reads. Duplicate samples were analyzed for each condition.
Contributor(s) Flavell RA, Rongvaux A, Harman CC
Citation(s) 25525875
Submission date Dec 02, 2014
Last update date May 15, 2019
Contact name Christian Harman
Organization name Yale University
Department Genetics/Immunobiology
Lab Flavell Lab
Street address 300 Cedar Street, The Anlyan Center
City New Haven
State/province Connecticut
ZIP/Postal code 06520
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (8)
GSM1557529 WT DMSO: alpha1 (replicate 1)
GSM1557530 WT DMSO: alpha7 (replicate 2)
GSM1557531 WT QVDOPH: alpha4 (replicate 1)
BioProject PRJNA269079
SRA SRP050448

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

Supplementary file Size Download File type/resource
GSE63794_geneIDs_sig_5fold.txt.gz 1.8 Kb (ftp)(http) TXT
GSE63794_gene_exp.diff.gz 8.3 Mb (ftp)(http) DIFF
GSE63794_genes.count_tracking.txt.gz 1.9 Mb (ftp)(http) TXT
GSE63794_genes.fpkm_tracking.gz 2.3 Mb (ftp)(http) FPKM_TRACKING
GSE63794_genes.read_group_tracking.txt.gz 5.1 Mb (ftp)(http) TXT 357 b (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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