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Global Identification of SYT-SSX2 Downstream Genes using Human Pluripotent Stem Cells

ABSTRACT: We established human pluripotent stem cell (PSC) lines expressing Synovial Sarcoma-specific oncogene, SYT-SSX2, under the control of doxycycline with dose- and time-dependent manner. Gene expression profiles were analyzed to identify early response genes of SYT-SSX2. SYT-SSX2-inducible PSC lines including two hESCs and one hiPSC were analyzed at several time points (0, 6, 12, 18, 24 hours) after doxycycline treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: Junya Toguchida

PROVIDER: E-GEOD-43080 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Global Identification of SYT-SSX2 Downstream Genes using Human Pluripotent Stem Cells

Project description:We established human pluripotent stem cell (PSC) lines expressing Synovial Sarcoma-specific oncogene, SYT-SSX2, under the control of doxycycline with dose- and time-dependent manner. Gene expression profiles were analyzed to identify early response genes of SYT-SSX2.

2013-01-30 | GSE43080 | GEO

Comparisons of transcriptome among several human iPSC clones derived from different origin and different donors

Project description:Genetically matched human iPSCs from different origins were generated using bone marrow stromal cells and dermal fibroblasts of the same donor, and the global gene expression profile were analyzed. Comparison of gene expressions among 14 iPS clones, 4 and 4 were derived from bone marrow stromal cells(BM), 2 and 4 were from dermal skin fibroblasts(SF) of donor90 and 91, respectively.

2013-01-01 | E-GEOD-41202 | biostudies-arrayexpress

Expression data from synovial sarcoma-like tumors induced in a genetically engineered mouse model

2009-04-14 | GSE14469 | GEO

A stage-specific induction system reveals that the oncogenic fusion protein in synovial sarcoma, SS18-SSX, is a cellular context-dependent epigenetic modifier

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

Rapid and efficient transdifferentiation into functional myocytes from human induced pluripotent stem cells (hiPSCs).

Project description:HiPSCs and human myoblast cells were differentiated into myocytes, and the global gene expression profile were analyzed. Comparison of gene expressions among 8 experiments, 3 were derived from hiPSCs(cell line; 253G1), 1 was derived from hiPSCs(cell line; 253G4), 1 was derived from hiPSCs(cell line; 201B7), 2 were from human myoblast cell line (Hu5/E18) and 1 was undifferentiated hiPSCs.

2013-04-01 | E-GEOD-43183 | biostudies-arrayexpress

Transcription profiling of synovial sarcoma-like tumors induced in a genetically engineered mouse model

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

Genomewide occupancy of the synovial sarcoma-associated SYT-SSX2 oncoprotein in C2C12 myoblasts

2011-09-26 | GSE26564 | GEO

Genomewide occupancy of the synovial sarcoma-associated SYT-SSX2 oncoprotein in C2C12 myoblasts

Project description:Synovial sarcoma is a rare malignancy that is characterized by the presence of a chromosomal translocation t(X;18). This genetic abnormality results in the fusion of 2 transcriptional co-regulators, SYT and SSX, which have been shown to mediate transcriptional activation and repression, respectively. Although the fusion protein does not bind DNA directly, SYT-SSX2 is known to function through interaction with chromatin-modifying complexes. In this study, we wanted to determine the SYT-SSX2 occupancy across the whole genome in order to further characterize its function by identifying genes that may be deregulated by this protein. C2C12 myoblasts were infected with retrovirus carrying SYT-SSX2-HA-FLAG expression vector. Chromatin immunoprecipitation (ChIP) was performed on cell lysates with either control IgG antibody (Abcam) or anti-FLAG antibody (Sigma). Lysates from 2 independent infections were pooled and used to isolate control ChIP DNA (IgG). DNA from 2 independent FLAG ChIP experiments (each using lysates from 2 independent infections) was pooled for SYT-SSX2 ChIP.

2011-09-26 | E-GEOD-26564 | biostudies-arrayexpress

Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2

Project description:Cellular identity is determined by its gene expression programs. The ability of the cell to change its identity and produce cell types outside its lineage is achieved by the activity of transcription controllers capable of reprogramming differentiation gene networks. The synovial sarcoma associated protein, SYT-SSX2, reprograms myogenic progenitors and human bone marrow-derived mesenchymal stem cells (BMMSCs) by dictating their commitment to a pro-neural lineage. It fulfills this function by directly targeting an extensive array of neural-specific genes as well as genes of developmental pathway mediators. Concomitantly, the ability of both myoblasts and BMMSCs to differentiate into their normal myogenic and adipogenic lineages was compromised. Synovial sarcoma is believed to arise in mesenchymal stem cells where formation of the t(X;18) translocation product, SYT-SSX, constitutes the primary event in the cancer. SYT-SSX is therefore believed to initiate tumorigenesis in its target stem cell. The data presented here allow a glimpse at the initial events that likely occur when SYT-SSX2 is first expressed and its dominant function in subverting the nuclear program of the stem cell, leading to its aberrant differentiation, as a first step toward transformation. In addition, we identified the fibroblast growth factor receptor gene, Fgfr2, as one occupied and upregulated by SYT-SSX2. Knockdown of FGFR2 in both BMMSCs and synovial sarcoma cells abrogated their growth and attenuated their neural phenotype. These results support the notion that the SYT-SSX2 nuclear function and differentiation effects are conserved throughout sarcoma development and are required for its maintenance beyond the initial phase. They also provide the stem cell regulator, FGFR2 as a promising candidate target for future synovial sarcoma therapy. This SuperSeries is composed of the SubSeries listed below.

2011-09-26 | GSE26565 | GEO

Gene expression profile of SYT-SSX2-expressing C2C12 myoblasts

Project description:Synovial sarcoma is a rare malignancy characterized by the presence of a specific chromosomal translocation t(X;18) that results in the formation of a fusion protein SYT-SSX. Because it is believed that synovial sarcoma arises from mesenchymal stem or progenitor cells, we wanted to determine the changes in gene expression caused by SYT-SSX2 in untransformed mesenchymal progenitor cells - murine C2C12 myoblasts in this experiment.

2011-09-26 | GSE26562 | GEO

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