 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 20, 2017 |
| Title |
Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments (CCFs) in senescent cells. The activation of cGAS, in turn triggers the production of SASP factors via Stimulator of interferon genes (STING), thereby promoting paracrine senescence. We demonstrate that diverse stimuli of cellular senescence engage the cGAS-STING pathway in vitro and we show cGAS-dependent regulation of senescence upon irradiation and oncogene activation in vivo. Our findings provide insights into the mechanisms underlying cellular senescence by establishing the cGAS-STING pathway as a crucial regulator of senescence and the SASP.
|
| |
|
| Overall design |
Primary WT MEFs and cGAS KO MEFs were passaged for three weeks under 20% oxygen; their RNA was isolated at three different time points (day 33, 36, 42) and processed for RNA sequencing.
|
| |
|
| Contributor(s) |
Glück S, Guey B, Gulen MF, Wolter K, Kang T, Bridgeman A, Schmacke NA, Rehwinkel J, Zender L, Ablasser A |
| Citation(s) |
28759028 |
| |
| Submission date |
Jun 16, 2017 |
| Last update date |
May 31, 2019 |
| Contact name |
Selene Glück |
| E-mail(s) |
selene.glueck@epfl.ch
|
| Organization name |
EPFL
|
| Department |
SV-GHI
|
| Lab |
Ablasser
|
| Street address |
Station 19
|
| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (24)
|
|
| Relations |
| BioProject |
PRJNA390720 |
| SRA |
SRP109350 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE100102_Genes_expression_GEO.txt.gz |
7.5 Mb |
(ftp)(http) |
TXT |
| GSE100102_cGAS-WT.logFC.xlsx |
885.3 Kb |
(ftp)(http) |
XLSX |
| GSE100102_transcripts_expression_GEO.txt.gz |
16.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...