CITE-seq of Ewing sarcoma lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE236284 | GEO | 2023/07/10
REPOSITORIES: GEO
Similar Datasets
Project description:Posterior homeobox D genes, in particular HOXD13, are over-expressed by Ewing sarcoma, a tumor driven by the oncogenic fusion protein EWS-FLI1. Here, we have found that EWS-FLI1 maintains HOXD13 expression through a GGAA microsatellite enhancer in the developmental posterior HOXD regulatory domain. Activation of this enhancer is EWS-FLI1 dependent and epigenomic silencing of this region leads to loss of HOXD13 expression in Ewing sarcoma cells, but not in unrelated cells. To determine the function of HOXD13 activation in Ewing sarcoma we performed nascent RNA sequencing upon HOXD13 knockdown. We identified NT5E as a target induced by HOXD13. NT5E encodes for the cell surface marker CD73, so we used CITE-seq to profile these cells.
2022-06-28 | GSE165973 | GEO
Project description:CD73 marks cells with increased mesenchymal morphologies and phenotypes. To understand the transcriptional differences in CD73+ and - cells, we performed bulk RNA-seq on the CD73 sorted cells. In this study, we investigated if and how transcriptional heterogeneity of EwS cells contributes to heterogeneity of tumor phenotypes in vivo. Digital spatial profiling and human whole transcriptome analysis interrogated transcriptomic heterogeneity in EwS CHLA10 cell line xenografts.
2023-07-10 | GSE226562 | GEO
Project description:EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma [CITE-seq]
| PRJNA698816 | ENA
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 cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor. Experiment Overall Design: Ewing tumors and EWS-FLI-1 inhibited cell lines were profiled on Affymetrix U133A (GPL96) arrays.
2008-06-15 | E-GEOD-7007 | biostudies-arrayexpress
Project description:Label-free 1DLC-MS analysis of cell lines and cell line derived small extracellular vesicles (sEVs) with duplicate injections. Goal to determine shared and distinct features of these tumor cells and their respective sEVs. Samples included analyzed EWS cells with different EWS-ETS fusions (EWS-FLI1 type I, II, and III and EWS-ERG) and their corresponding sEVs. Non-EWS controls included osteosarcoma, rhabdomyosarcoma, and benign cells, i.e., osteoid osteoma and mesenchymal stem cells.
2022-10-31 | MSV000090623 | MassIVE
Project description:Ewing sarcoma (EWS) is a malignant pediatric bone cancer. Most Ewing sarcomas are driven by EWS-FLI1 oncogenic transcription factor that plays roles in transcriptional regulation, DNA damage response, cell cycle checkpoint control, and alternative splicing. USP1, a deubiquitylase which regulates DNA damage and replication stress responses, is overexpressed at both the mRNA and protein levels in EWS cell lines compared to human mesenchymal stem cells, the EWS cell of origin. The functional significance of high USP1 expression in Ewing sarcoma is not known. Here, we identify USP1 as a transcriptional target of EWS-FLI1 and a key regulator of EWS cell survival. We show that EWS-FLI1 knockdown decreases USP1 mRNA and protein levels. ChIP and ChIP-seq analyses show EWS-FLI1 occupancy on the USP1 promoter. Importantly, USP1 knockdown or inhibition arrests EWS cell growth and induces cell death by apoptosis. We observe destabilization of Survivin (also known as BIRC5 or IAP4) and activation of caspases-3 and -7 following USP1 knockdown or inhibition in the absence of external DNA damage stimuli. Notably, EWS cells display hypersensitivity to combinatorial treatment of doxorubicin or etoposide, EWS standard of care drugs, and USP1 inhibitor compared to single agents alone. Together, our study demonstrates that USP1 is regulated by EWS-FLI1, the USP1-Survivin axis promotes EWS cell survival, and USP1 inhibition sensitizes EWS cells to standard of care chemotherapy.
2024-01-26 | PXD041033 | Pride
Project description:Ewing sarcoma (EwS) is an adolescent and young adult sarcoma characterized by chromosome translocations between members of the FET family of RNA binding proteins and members of the ETS family of transcription factors, the most frequent fusion being EWS-FLI1. EWS-FLI1 acts as a pioneer factor, creating de novo enhancers and activating genes located in the vicinity of EWS-FLI1-bound microsatellite sequences. recent results from our lab indicate that EWS-FLI1, which activates transcription through binding to the DNA at specific sites, can generate fully novel, unconventional transcription units in regions of the genome that are fully quiescent in normal cells (manuscript in preparation). The hypothesis of the project is that the open reading frames (ORFs) of these transcripts may encode peptides presented at the cell surface by HLA class I molecules and hence be recognized as non-self by the immune system. The aim of this study is to detect Ewing-specific neo-peptides/proteins using proteomics approach.
2022-05-12 | PXD027309 | Pride
Project description:Poly(ADP-ribose) polymerase 1 (PARP1) critically facilitates DNA damage response (DDR) that suppresses genomic instability. However, the physiological function of PARP1 in regulating genomic integrity is unclear. We investigated the Ewing’s sarcoma breakpoint region 1 (EWS) and found that it regulated the physiological function of PARP1. EWS was indispensable to dissociation of PARP1 from damaged DNA, promoting DDR and regulating DDR protein expression. Abnormal PARP1 accumulation due to EWS expression silencing, induced hyper-PARylation, which exhausted cellular NAD+ levels and caused cell death in in vitro and in vivo. Positively charged EWS arginine-glycine-glycine (Arg-Gly-Gly, RGG) domains directly interact with poly ADP-ribose (PAR) chains produced by PARP1 and are essential to dissociate PARP1 from damaged DNA. Consistently, Ewing’s sarcoma cells with defective EWS function accumulated PARP1 on chromatin and tissues from Ewing’s sarcoma patients, exhibiting high PARylation levels. Taken together, loss of EWS causes defects in PARP1 dissociation and results in genomic instability.
2020-11-03 | PXD016145 | Pride
Project description:Ewing sarcoma (EWS) is an aggressive pediatric bone tumor characterized by unmet clinical needs and an incompletely understood epigenetic heterogeneity. Here we considered CD99, a major surface molecule hallmark of EWS malignancy. Fluctuations of CD99 expression strongly impair cell dissemination, differentiation, and death. CD99 is also loaded within extracellular vesicles (EVs) and the delivery of CD99 positive or CD99 negative EVs dynamically exerts oncogenic or oncosuppressive functions to recipient cells, respectively. We undertook mass spectrometry and functional annotation analysis to investigate the consequences of CD99 silencing on the proteomic landscape of EWS cells and related EVs. Our data demonstrate that i. the decrease of CD99 leads to major changes in the proteomic profile of EWS cells and EVs; ii. intracellular and extracellular compartments display two distinct signatures of differentially expressed proteins; iii. proteomic changes converge to the modulation of cell migration and immune-modulation biological processes; iv. CD99-silenced cells and related EVs are characterized by a migration-suppressive, pro-immunostimulatory proteomic profile. Overall, our data provide a novel source of CD99-associated protein biomarkers to be considered for further validation as mediators of EWS malignancy and as EWS disease liquid biopsy markers.
2024-05-22 | PXD046846 | Pride