Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141889 | GEO | 2022/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Modeling the initiation of Ewing sarcoma tumorigenesis in differentiating human embryonic stem cells.

Project description:Oncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. However, despite the well-established role of EWS-FLI1 in tumor initiation, the development of models of Ewing sarcoma in human cells with defined genetic elements has been challenging. Here, we report a novel approach to model the initiation of Ewing sarcoma tumorigenesis that exploits the developmental and pluripotent potential of human embryonic stem cells. The inducible expression of EWS-FLI1 in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. Furthermore, these cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth, which is a hallmark of Ewing sarcoma tumors.

| S-EPMC4829493 | biostudies-literature

Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [RNA-seq]

Project description:Ewing sarcoma family of tumors (ESFT) is a uniquely human, highly aggressive bone and soft tissue malignancy peaking during adolescence characterized by EWSR1/ETS rearrangements. EWSR1/FLI1 expression is only tolerated in embryonic and mesenchymal stem cells (hESC and hMSC, respectively) that, although acquire ESFT transcriptional signatures, are devoid of tumorigenic potential. Here we report that ectopic EWSR1/FLI1 expression in hESC allows in vivo differentiation towards the three germ layers. In vitro, teratoma-derived hMSCs are devoid of transformation abilities. In vivo, these hMSCs led to the generation of T-cell lymphomas and ESFT-like tumors, composed of small-round blue cells. This new experimental approach constitutes a testing bench for the biology of translocation-dependent developmental tumors, from acute lymphoblastic leukemia to a variety of sarcomas.

2022-12-31 | GSE141888 | GEO

Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [expression array]

2022-12-31 | GSE140328 | GEO

De novo modeling of chromoplectic Ewing sarcoma tumors from patient-derived mesenchymal stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-18 | GSE150783 | GEO

Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells

Project description:Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells

| PRJNA595097 | ENA

Ewing Sarcoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2012-09-01 | GSE36859 | GEO

Genome-wide chromatin analysis of Ewing sarcoma

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-10-30 | E-GEOD-61953 | biostudies-arrayexpress

Modeling initiation of Ewing sarcoma in human neural crest cells.

Project description:Ewing sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC) and/or neural crest (NCSC) stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC). Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC) progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis.

| S-EPMC3084816 | biostudies-literature

Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [RNA-seq]

Project description:Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [RNA-seq]

| PRJNA595101 | ENA

Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [expression array]

Project description:Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [expression array]

| PRJNA589297 | ENA