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Title: Dll1 acts as a tumor suppressor in neural stem cells to induce an astroglial lineage-restricted glioblastoma      
keywords:
Transcriptome or Gene expression
ID:
PRJNA146365
description:
There is increasing evidence for tissue stem cells as potential source for cancers. However, the cellular and molecular mechanisms at the origin of this transformation remain elusive. Here we show that Delta-like1 (Dll1) mutation induces the oncogenic transformation of neural stem cell–derived neurospheres into oncogenic spheres capable of generating histological and molecular human glioblastoma (GBM)-like tumors upon subcutaneous and intracranial transplantations into nude mice. Serial transplantation assays suggest that Dll1 spheres tumorigenicity results from the oncogenic transformation of normal neural stem cell into GBM-producing stem cell. Compared differentiation of Dll1 vs. WT spheres shows the presence in Dll1 spheres of a subpopulation of cells which although fated to a glial lineage fail to differentiate terminally, in keeping with the astrocytic promoting function of Delta-Notch. This population of astrocyte progenitors proliferates actively and fails to down-regulate EGFR phosphorylation. These studies suggest that Dll1-induced tumorigenesis is restricted to the astrocytic lineage thereby providing a model for human GBM as well as an explanation for the duality of Notch signaling acting either as an oncogene or a tumor suppressor in stem/progenitor cells derived tumors, depending on the lineage commitment. Overall design: Comparison between control (WT) and mutants (Dll1-3 and Dll1-5) cells was performed. Two biological replicates (n=3 each replicate) were used, and each replicate (n=3, total RNA pooled) was dye-swaped.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA146365
authentication:
none
authorization:
none
dateReleased:
09-24-2011
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject