Project name: Mus musculus

Description: Ewing’s sarcoma is highly malignant bone tumor that involves childhood and adolescent, and its nature has not been well understood. To clarify its cellular origin and the mechanisms of tumorigenesis, we used ex vivo approach to create a murine model for Ewing’s sarcoma. The osteochondrogenic progenitors derived from the embryonic superficial zone (eSZ, designated as FZ in the data set) of murine long bones at late gestation were purified by microdissection, introduced with EWS-FLI1 or EWS-ERG retroviruses and transplanted into nude mice. Ewing’s sarcoma-like small round cell sarcoma developed at 100% penetrance, whereas tumor induction was less effective when growth place (GP)-derived cells were used. The different response of gene expression to EWS-FLI1 between eSZ and GP cells suggests importance of the specific cellular context for EWS-FLI1 to induce Ewing’s sarcoma. The Wnt/β-catenin pathway was involved in close relationship to the cellular context, with Dkk2 and Wipf1 as important downstream modulators. Furthermore, gene expression profiling revealed similarity between our models and human Ewing’s sarcoma. These results indicate that Ewing’s sarcoma originates from the embryonic osteochondrogenic progenitor.Overall design: We purified eSZ and GP cells by microdissection from dpc 18.5 murine embryo. The purified eSZ cells were mildly digested by collagenase and their osteochondrogenic potency was confirmed by in vitro differentiation assay. Retrovirus-mediated gene transfer of EWS-FLI1 or EWS-ERG was then carried out and transduction efficiency was exhibited by FACS analyses. The relationship between cellular context and EWS-FLI1 is important, given the strict limitation for the origin of mouse Ewing’s sarcoma. Gene expression profiles were therefore compared between eSZ and GP cells in the presence or absence of EWS-FLI1.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2011-10-04