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Series GSE73753 Query DataSets for GSE73753
Status Public on Apr 05, 2016
Title Expression data of endothelial cells from mouse hindbrain and genetic Wnt-medulloblastoma and Shh-medulloblastoma mouse models
Organism Mus musculus
Experiment type Expression profiling by array
Summary The childhood brain tumour medulloblastoma includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant Beta-Catenin in WNT-medulloblastoma – an essentially curable form of the disease – induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoural chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma – a less curable disease subtype – contains an intact blood brain barrier, rendering this tumour impermeable and resistant to chemotherapy. Remarkably, the medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumour vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumours.
We used microarrays to detail the global program of gene expression within endothelial cells from normal mouse hindbrain and genetic mouse models of different medulloblastoma subtypes to identify and verify up-regulated and down-regulated genes
 
Overall design Endothelial cells were isolated from adult mouse hindbrain and genetic mouse models of Wnt and Shh-medulloblastoma using Cd-144 and Cd-105 antibodies based magnetic sorting. RNA was extracted and used for hybridization on Affymetrix microarrays. We sought to identify changes in endothelial gene expression patterns based on the surrounding microenvironment, so we purified endothelial cells from normal mouse brain or tumors from genetic mouse models. These include the Shh-medulloblastoma model (Ptch+/-; Ink4c -/-) and Wnt-medulloblastoma model (Blbp-Cre; mutant Ctnnb1+/-; p53-/-; mutant Pik3ca +/-)
 
Contributor(s) Phoenix T, Gilbertson R
Citation(s) 27050100
Submission date Oct 05, 2015
Last update date Feb 21, 2018
Contact name David Finkelstein
E-mail(s) david.finkelstein@stjude.org
Phone 9014953931
Organization name St Jude Children's Research Hospital
Department Computational Biology
Street address 332 N. Lauderdale St.
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (24)
GSM1902106 adult hindbrain endothelial cells, biological rep1
GSM1902107 adult hindbrain endothelial cells, biological rep2
GSM1902108 adult hindbrain endothelial cells, biological rep3
Relations
BioProject PRJNA297815

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Supplementary file Size Download File type/resource
GSE73753_RAW.tar 226.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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