Transcriptional programs define intratumoral heterogeneity of Ewing sarcoma at single cell resolution
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ABSTRACT:
PROVIDER: PRJNA533603 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8832670.fastq.gz | Fastqsanger.gz | |||
| SRR8832671.fastq.gz | Fastqsanger.gz | |||
| SRR8832672.fastq.gz | Fastqsanger.gz | |||
| SRR8832673.fastq.gz | Fastqsanger.gz | |||
| SRR8832674.fastq.gz | Fastqsanger.gz |
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Project description:Adane B, Alexe G, Seong BKA, Lu D, Hwang E, Hnisz D, Lareau CA, Ross L, Lin S, Dela Cruz FS, Richardson M, Weintraub AS, Wang S, Balboni-Iniguez A, Dharia NV, Conway AS, Robichaud AL, Tanenbaum B, Krill-Burger JM, Vazquez F, Schenone M, Berman JN, Kung A, Carr SA, Aryee MJ, Young RA, Crompton BD, Stegmaier K. 2021 Cancer Cell.
The core cohesin subunit STAG2 is recurrently mutated in Ewing sarcoma but its biological role is less clear. Herein, we demonstrate that cohesin complexes containing STAG2 occupy enhancer and polycomb repressive complex (PRC2) marked regulatory regions. Genetic suppression of STAG2 leads to a compensatory increase in cohesin-STAG1 complexes, but not in enhancer rich regions, and results in reprogramming of cis-chromatin interactions. Strikingly, in STAG2 knockout cells, the oncogenic genetic program driven by the fusion transcription factor EWS/FLI1 was highly perturbed, in part due to altered enhancer-promoter contacts. Moreover, loss of STAG2 also disrupted PRC2-mediated regulation of gene expression. Combined, these transcriptional changes converged to modulate EWS/FLI1, migratory and neurodevelopmental programs. Finally, consistent with clinical observations, functional studies revealed that loss of STAG2 enhances the metastatic potential of Ewing sarcoma xenografts. Our findings demonstrate that STAG2 mutations can alter chromatin architecture and transcriptional programs to promote an aggressive cancer phenotype.
| MSV000082954 | MassIVE
Project description:The study aims to define gene expression changes associated with mithramycin treatment of Ewing Sarcoma cell lines.
2011-04-18 | GSE25127 | GEO
Project description:We identify and validate an Ewing sarcoma-specific CRC, which is under control of EWS-FLI1. Formed by KLF15, TCF4 and NKX2-2, this CRC apparatus coordinates the gene expression programs in Ewing sarcoma cells. These data advance the understanding of the mechanistic basis of transactional dysregulation in Ewing sarcoma, and provide potential novel therapeutic strategies against this malignancy.
2020-09-29 | GSE141493 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE36857: Goldengate Methylation analysis: Ewing Sarcoma GSE36858: 5- AZA treatment of EWS cell lines Refer to individual Series
2012-09-01 | E-GEOD-36859 | biostudies-arrayexpress
Project description:The study aims to define gene expression changes associated with mithramycin treatment of Ewing Sarcoma cell lines. The data consist of 12 arrays. Two cell lines, TC71 and TC32, were treated with solvent control or with mithramycin, and RNA was extracted at 6 hours. Three biological replicates per cell line/treatment.
2011-04-18 | E-GEOD-25127 | biostudies-arrayexpress
Project description:Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma. RNA-seq to compare transcriptiome of control A673 ewing sarcoma cells stably expression a non-target or RUNX3 shRNA
2014-05-01 | E-GEOD-56900 | biostudies-arrayexpress
Project description:The expression profile of primary pediatric Ewing sarcoma (ES) and osteosarcoma (OS) were analyzed. 8 Ewing sarcoma patient samples (TUM-ES0XXX) and 10 osteosarcoma patient samples (TUM-OS0XXX) were analyzed.
2016-07-05 | E-GEOD-73166 | biostudies-arrayexpress
Project description:Study of promoter methylation of ewing sarcoma cell lines and mesenchymal stem cell from ewing sarcoma patients and healthy donors
2018-10-24 | GSE118872 | GEO
Project description:Tumor: tumor microenvironment (TME) interactions are critical for tumor progression and the composition and structure of the local extracellular matrix (ECM) are key determinants of tumor metastasis. We recently reported that activation of Wnt/beta- catenin signaling in Ewing sarcoma cells induces widespread transcriptional changes that are associated with acquisition of a metastatic tumor phenotype. Significantly, ECM protein-encoding genes were found to be enriched among Wnt/beta-catenin induced transcripts, leading us to hypothesize that activation of canonical Wnt signaling might induce changes in the Ewing sarcoma secretome. To address this hypothesis, conditioned media from Ewing sarcoma cell lines cultured in the presence or absence of Wnt3a was collected for proteomic analysis. Label-free mass spectrometry was used to identify and quantify differentially secreted proteins. We then used in silico databases to identify only proteins annotated as secreted. Comparison of the secretomes of two Ewing sarcoma cell lines revealed numerous shared proteins, as well as a degree of heterogeneity, in both basal and Wnt-stimulated conditions. Gene set enrichment analysis of secreted proteins revealed that Wnt stimulation reproducibly resulted in increased secretion of proteins involved in ECM organization, ECM receptor interactions, and collagen formation. In particular, Wnt-stimulated Ewing sarcoma cells upregulated secretion of structural collagens, as well as matricellular proteins, such as the metastasis-associated protein, tenascin C (TNC). Interrogation of published databases confirmed reproducible correlations between Wnt/beta-catenin activation and TNC and COL1A1 expression in patient tumors. In summary, this first study of the Ewing sarcoma secretome reveals that Wnt/beta-catenin activated tumor cells upregulate secretion of ECM proteins. Such Wnt/beta-catenin mediated changes are likely to impact on tumor: TME interactions that contribute to metastatic progression.
2018-02-07 | PXD007909 | Pride