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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 26, 2011 |
| Title |
Reprogramming of mesenchymal stem cells by the synovial sarcoma-associated oncogene SYT-SSX2 |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by array
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| Summary |
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.
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| Overall design |
Refer to individual Series
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| Contributor(s) |
Garcia CB, Eid JE |
| Citation(s) |
21996728, 22594313 |
| Submission date |
Jan 11, 2011 |
| Last update date |
Aug 14, 2019 |
| Contact name |
Josiane Eid |
| E-mail(s) |
josiane.eid@vanderbilt.edu
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| Organization name |
Vanderbilt University
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| Street address |
2220 Pierce Avenue
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| City |
Nashville |
| ZIP/Postal code |
37232 |
| Country |
USA |
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| Platforms (3) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (10)
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| This SuperSeries is composed of the following SubSeries: |
| GSE26562 |
Gene expression profile of SYT-SSX2-expressing C2C12 myoblasts |
| GSE26563 |
Gene expression profile of SYT-SSX2-expressing human bone marrow-derived mesenchymal stem cells |
| GSE26564 |
Genomewide occupancy of the synovial sarcoma-associated SYT-SSX2 oncoprotein in C2C12 myoblasts |
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| Relations |
| BioProject |
PRJNA136229 |
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