Mouse Synovial Sarcoma Models
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71843 | GEO | 2016/07/01
SECONDARY ACCESSION(S): PRJNA292306
REPOSITORIES: GEO
Similar Datasets
Project description:Compare transcriptomes from SS18-SSX1 and SS18-SSX2 tumors 6 tumors analyzed, 3 from each genotype, all initiated by TATCre injection
2016-07-01 | E-GEOD-71843 | biostudies-arrayexpress
Project description:Transcriptome comparisons by RNAseq of genetically engineered mouse models of synovial sarcoma, expressing SS18-SSX1 or SS18-SSX2 and having homozygous conditional genetic silencing of Pten or wildtype Pten.
2016-11-03 | GSE81476 | GEO
Project description:SS18-SSX fusion proteins play a central role in synovial sarcoma development, however, genetic network and mechanisms of synovial sarcomagenesis remain largely unknown. To clarify such unknown mechanisms, we have established a new ex vivo mouse model for synovial sarcoma, using retrovirus-mediated gene transfer of SS18-SSX1 to mouse embryonic mesenchymal cells followed by subcutaneous transplantation into nude mice. This approach successfully induced subcutaneous tumors in 100% of recipients, showing invasive proliferation of short spindle tumor cells with occasional biphasic appearance. Cytokeratin expression was observed in epithelial components in tumors and expression of TLE1 and BCL2 was also shown. Gene expression profiling indicates modulation of the SWI/SNF pathway by introduction of SS18-SSX1 into mesenchymal cells, and upregulation of Tle1 and Atf2 in tumors. Collectively, these findings indicate the model exhibits typical phenotypes of human synovial sarcoma. Retroviral tagging of the tumor identified 15 common retroviral integration sites with the Dnm3 locus as the most frequent in 30 mouse synovial sarcomas. Up-regulation of micro RNAs miR-199a2 and miR-214 within the Dnm3 locus was observed. Co-introduction of SS18-SSX1 and miR-214 indeed accelerated sarcoma onset, indicating that miR-214 is a cooperative onco-miR in synovial sarcomagenesis. miR-214 functions in the cell non-autonomous manner, promoting cytokine gene expression such as Cxcl15/IL8. We have succeeded to generate a novel mouse model for human synovial sarcoma. As miR-214 overexpression in human synovial sarcoma was reported, our results underscore the important role of miR-214 in tumor development and disease progression. We used microarrays to detail the global program of gene expression in mouse synovial sarcoma and embryonic mesenchymal cells
2020-03-30 | GSE141251 | GEO
Project description:Synovial sarcoma is a deadly soft-tissue malignancy with a predilection for adolescents and young adults. Mice recapitulate synovial sarcomagenesis from expression of SS18-SSX2 in certain cells. Concomitant expression of a stabilized form of beta-catenin enhances synovial sarcomagenesis and expands the potential cells of origin. Mice bearing conditional expression of SS18-SSX2 from the Rosa26 locus and conditional excision of the 3rd exon of beta-catenin, each activated in the leg by Cre-recombinase expressed from an adeno-associated viral vector, formed large tumors at brief latency.
2015-11-04 | E-GEOD-47388 | biostudies-arrayexpress
Project description:We analyzed the effects of cellular context on the function of the synovial sarcoma-specific fusion protein, SS18-SSX, using human pluripotent stem cells containing the drug-inducible SS18-SSX gene. To investigate the cell-type-dependent effecfts of SS18-SSX, we performed gene expression profiling experiments. Comparison of global gene expressions of hPSCs, hPSC-NCCs, and hPSC-MSCs with or without the inductuion of SS18-SSX2
2016-04-13 | E-GEOD-63895 | biostudies-arrayexpress
Project description:The cancer-specific fusion oncoprotein SS18-SSX1 disturbs chromatin accessibility by hijacking the chromatin-remodeling BAF complex from the promoters or enhancers to the H2AK119Ub-marked polycomb-repressed chromatin regions. Relocation of the BAF complex was achieved through selective recognition of the H2AK119Ub nucleosomes by the synovial sarcoma X breakpoint 1 protein SSX1, which neither has a ubiquitin (Ub)-binding domain nor binds to free Ub. To elucidate the mechanism by which SSX1 selectively recognizes H2AK119Ub nucleosomes, here we report the cryo-EM structure of SSX1 bound to H2AK119Ub nucleosomes at a resolution of 3.1 Å. The structure reveals that the SSX1 N-terminal basic region (residues W164, R167, L168, R169) is anchored to the H2A/H2B acidic patch, while the aromatic amino acid (residue Y177) in the middle of SSX1 interacts with the hydrophobic pocket formed by the H2A α2 and α3 helixes. Ub recognition by SSX1 is unique and depends on a cryptic basic groove formed by H3 (residues R49, R52, K56) and the Ub motif (residues R42, R72, R74) on the H2AK119 site. Our results describe a novel mode of site-specific ubiquitinated nucleosome recognition that underlies the specific hijacking of the BAF complex to polycomb regions by SS18-SSX1 in synovial sarcoma.
2023-09-04 | GSE236811 | GEO
Project description:Synovial sarcoma-like tumors were generated in mice by conditionally expressing the human t(X;18) translocation-derived SYT-SSX2 fusion protein. Using a Tamoxifen-inducible CreER system, we show here that sporadic expression of SYT-SSX2 across multiple tissue types leads to exclusive formation of synovial sarcoma-like tumors while its widespread expression is lethal. CreER-based sporadic expression both avoids the severe early developmental phenotypes associated with widespread SYT-SSX2 expression and better models natural pathogenesis of cancers where transformed cells usually arise within an environment of largely normal cells.
2009-04-14 | GSE14469 | GEO
Project description:A novel mouse model for human synovial sarcoma expressing SS18-SSX1
| PRJNA592959 | ENA
Project description:Synovial sarcoma-like tumors were generated in mice by conditionally expressing the human t(X;18) translocation-derived SYT-SSX2 fusion protein. Using a Tamoxifen-inducible CreER system, we show here that sporadic expression of SYT-SSX2 across multiple tissue types leads to exclusive formation of synovial sarcoma-like tumors while its widespread expression is lethal. CreER-based sporadic expression both avoids the severe early developmental phenotypes associated with widespread SYT-SSX2 expression and better models natural pathogenesis of cancers where transformed cells usually arise within an environment of largely normal cells. Experiment Overall Design: Genetically engineered mice capable of conditionally expressing the human synovial sarcoma-associated SYT-SSX2 fusion oncogene were mated with genetically engineered mice expressing the CreER fusion protein from ROSA locus. The progenies harboring both CreER and SYT-SSX2 were followed up with or without tamoxifen injection. Tumors were generated in these mice that were dissected out, RNA extracted, and subjected to expression profiling by microarray analysis.
2009-04-24 | E-GEOD-14469 | biostudies-arrayexpress
Project description:Using affinity purification determine changes in SS18 BAF complex upon fusion to SSX1. Using soluble nuclear fraction (nuclear extract NE) and nuclease digested chromatin fraction (CHR) we performed affinity capture of proteins bound to wild type SS18 and synovial sarcoma SS18-SSX1 fusion from NE and CHR of 293T cells.
2020-08-09 | PXD018715 | Pride