Transcriptomics

Dataset Information

0

A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors


ABSTRACT: Embryonal Tumors with Multilayered Rosettes (ETMRs) have recently been described as a new entity of rare pediatric brain tumors with fatal outcome. We show here that ETMRs are characterized by a parallel activation of Shh- and Wnt-signaling. Co-activation of these pathways in murine neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts based on histology and global gene expression analyses, and point to apical radial glia cells as the possible tumor cell-of-origin. Overexpression of LIN28A, which is a hallmark of human ETMRs, augments Sonic Hedgehog (Shh)- and Wnt-signaling in these precursor cells through downregulation of let7-miRNA, and LIN28A/let7a interaction with the Shh-pathway was detected at the level of Gli mRNA. Finally, human ETMR cells that were transplanted into immunocompromised host mice were responsive to the Shh-inhibitor Arsenic trioxide (ATO). Our findings provide a novel mouse model to study this tumor type, demonstrate the driving role of Wnt- and Shh-activation in the growth of ETMRs and propose downstream inhibition of Shh-signaling as a therapeutic option for patients with ETMRs. Gene expression data of hGFAP-cre::Ctnnb1(ex3)Fl/+SmoM2Fl/+ , hGFAP-cre::SmoM2Fl/+ , hGFAP-cre::Ctnnb1(ex3)Fl/+ and Control mice

ORGANISM(S): Mus musculus

PROVIDER: GSE103348 | GEO | 2017/09/11

SECONDARY ACCESSION(S): PRJNA401887

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2012-02-29 | E-GEOD-33199 | biostudies-arrayexpress
2024-04-17 | GSE241018 | GEO
2024-04-17 | GSE240627 | GEO
2008-06-20 | E-GEOD-10727 | biostudies-arrayexpress
2008-06-20 | E-GEOD-10728 | biostudies-arrayexpress
2008-06-20 | E-GEOD-10726 | biostudies-arrayexpress
2015-02-13 | E-GEOD-65888 | biostudies-arrayexpress
2022-02-15 | PXD028697 | Pride
2021-10-13 | GSE180477 | GEO
2021-11-18 | GSE175777 | GEO