Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Atrx deletion impairs cGAS-STING signaling and increases response to radiation and oncolytic herpesvirus in soft tissue sarcoma

ABSTRACT: RNA sequencing of isogenic ATRX wild-type (WT) and ATRX knockout (KO) paired isogenic cell lines treated with either 1.)interferon stimulatory DNA (ISD) and harvested 24 hours after treatment, 2)4 Gy ionizing radiation and harvested 36 hours after treatment, or 3) untreated control. These experiments help determine the differential impact of ATRX mutational status on cGAS-STING and type-I interferon signaling in soft tissue sarcoma.

ORGANISM(S): Mus musculus

PROVIDER: GSE165878 | GEO | 2021/02/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNA-sequencing of primary soft tissue sarcomas and cell lines with ATRX deletion

Project description:RNA sequencing of a primary tumors from a sarcoma genetically engineerted mouse model with activation of oncogenic Kras, deletion of p53 and deletion of Atrx, as compared to control sarcomas with identical genetic alterations but with wild-type Atrx. Tumors were either untreated or recieved 20 Gy of ionizing radiation and were harvested at 4 hrs, 3 day, or 6 day timepoints post treatment. For cell lines, isogenic ATRX wild-type (WT) and ATRX knockout (KO) paired isogenic cell lines treated with either 1.)interferon stimulatory DNA (ISD) and harvested 24 hours after treatment, 2)4 Gy ionizing radiation and harvested 36 hours after treatment, or 3) untreated control. These experiments help determine the differential impact of ATRX mutational status on cGAS-STING and type-I interferon signaling in soft tissue sarcoma.

2021-03-06 | GSE167537 | GEO

Characterization of open chromatin regions and ATRX, DAXX, H3.3 and cGAS binding sites in BJ-hTERT cells mutant for ATRX, on cGAS WT or null background

Project description:Mutations in the chromatin remodeller X-linked α-thalassaemia intellectual disability syndrome protein (ATRX) are a well-recognised cause of developmental problems in males. In two patients demonstrating white matter disease, intracranial calcification and learning difficulties, we identified a persistent upregulation of interferon stimulated gene expression, and the same Y1758C mutation in ATRX. We describe this substitution, and other ‘classical’ ATRX syndrome-associated loss-of-function mutations, to result in enhanced interferon signalling, and that while this effect is dependent on cGAS it is not mediated by cGAMP. Taking advantage of the retained expression of Y1758C mutant protein, we demonstrate a redistribution of mutant-ATRX/DAXX/H3.3 complex and cGAS at open chromatin in cGAS wild-type, but not in cGAS-null, cells. Thus, we show that ATRX is essential for the homeostatic control of type I interferon signalling, and that cGAS mediates differential genomic binding of mutant ATRX, and a preferential association with DAXX and H3.3 at accessible chromatin, leading to changes in gene expression.

2023-09-27 | GSE212919 | GEO

Profiling of SF188 ATRX isogenic glioma cells

Project description:Methylation profiling of SF188 paediatric high grade glioma cell line isogenic clones carrying CRISR/Cas9 frameshift deletions in ATRX

2019-06-01 | E-MTAB-7800 | biostudies-arrayexpress

Transcriptome analysis of ATRX and DAXX knockout mouse ESC

Project description:PolyA+ RNA-Seq was performed on wildtype, ATRX and DAXX knockout cells derived by CRISPR targeting (Sadic et. al, EMBO Rep, 16(7), p836-850, 2015, DOI: 10.15252/embr.201439937). PolyA+ RNA-Seq was performed on wildtype, ATRX and DAXX knockout cells derived by CRISPR targeting (Sadic et. al, EMBO Rep, 16(7), p836-850, 2015, DOI: 10.15252/embr.201439937). Cells (isogenic, male)

2015-10-26 | E-GEOD-73881 | biostudies-arrayexpress

Two opposing gene expression patterns within ATRX aberrant neuroblastoma

Project description:To study the role of distinct ATRX aberrations in neuroblastoma we created isogenic ATRX aberrant models using CRISPR-Cas9 in several neuroblastoma cell lines and one tumoroid. We created ATRX knock-out models, ATRX in-frame exon 2-10 deletions and ATRX in-frame exon 2-13 deletions. Additionally, we included patient-derived models data (i.e. cell line data and one tumoroid).

2023-03-16 | GSE226770 | GEO

Atrx deletion impairs cGAS-STING signaling and increases response to radiation and oncolytic herpesvirus in soft tissue sarcoma

Project description:Atrx deletion impairs cGAS-STING signaling and increases response to radiation and oncolytic herpesvirus in soft tissue sarcoma

| PRJNA698482 | ENA

Effect of ATRX deficiency on gene expression of RCAS-nTva derived murine gliomas [RNA-seq: ATRX_Immuno_cell_line]

Project description:To investigate the impact of ATRX loss on tumor microenvironment we generated ATRX-intact and -deficient tumors in immune competent mice with the RCA-nTva system. Mice were injected with a tumorigenic RCAS construct (PDGFa and shTP53) and an RCAS bearing CRE recombinase. This was performed in mice that were ATRX wt and ATRX floxed. Tumors were then harvested, processed, and cell lines were generated and cultured for downstream analysis.

2023-05-08 | GSE231830 | GEO

Synthetic lethal screen reveals selective vulnerability of ATRX-mutant cancers to WEE1 inhibition

Project description:we performed a genome-wide synthetic lethal screen, using CRISPR-Cas9 genome editing, to identify potential therapeutic targets specific for ATRX-mutated cancers. In isogenic hepatocellular carcinoma (HCC) cell lines engineered for ATRX loss, we identified 58 genes, including the checkpoint kinase WEE1, uniquely required for the cell growth of ATRX null cells. Treatment with the WEE1 inhibitor AZD1775 robustly inhibited the growth of several ATRX-deficient HCC cell lines in vitro, as well as xenografts in vivo. The increased sensitivity to the WEE1 inhibitor was caused by accumulated DNA damage induced apoptosis. AZD1775 also selectively inhibited the proliferation of patient-derived primary cell lines from gliomas with naturally occurring ATRX mutations, indicating that the synthetic lethal relationship between WEE1 and ATRX could be exploited in a broader spectrum of human tumors. As WEE1 inhibitors have been investigated in several phase II clinical trials, our discovery provides the basis for an easily clinically testable therapeutic strategy specific for cancers deficient in ATRX.

2019-10-23 | GSE114035 | GEO

Differential gene expression analysis at different stages of neuronal development in mutant and wild type ATRX cells

Project description:Investigating transcription deregulation and interferon signaling activation in iPSC-derived neurons deficient for ATRX.

2023-09-27 | GSE212922 | GEO

Epigenomic analysis of Atrx deficiency in murine glioma cells of orgin [Atrx ChIP]

Project description:The chromatin regulator ATRX is inactivated in large subsets of adult and pediatric glioma. Whether and how ATRX deficiency promotes oncogenesis by epigenomic dysregulation remains unclear. We found that Atrx loss, especially when coupled with Tp53 inactivation, promoted cell motility and modulated differentiation state in primary murine neuroepithelial progenitors, recapitulating characteristic disease phenotypes and molecular features. Moreover, Atrx deficiency induced widespread shifts in chromatin accessibility, histone composition, and gene transcription at vacant Atrx binding sites distributed across the genome. Finally, target genes mediating Atrx-deficient phenotypes in vitro exhibited similarly selective misexpression in ATRX-mutant human glioma tissues and cell lines. These findings demonstrate that, in appropriate physiological contexts, ATRX deficiency and its epigenomic sequelae are sufficient to induce disease-defining oncogenic phenotypes.

2017-12-31 | GSE100462 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data