Dataset Information

Gene expression data from postnatal day 7 subventricular zone (SVZ), IV ventricle and cerebellar white matter-derived neural stem cells (NSCs) and of cancer stem cells (CSCs) from Ptch het p53 wt and Ptch het p53 het mouse medulloblastomas

ABSTRACT: We exploited microarrays to detail the global program of gene expression underlying normal stem cells and cancer stem cells in the cerebellum and in medulloblastomas (MBs).

ORGANISM(S): Mus musculus

PROVIDER: GSE37316 | GEO | 2012/04/17

SECONDARY ACCESSION(S): PRJNA159433

REPOSITORIES: GEO

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Project description:Medulloblastomas (MBs) are the most common brain tumors in children. Some are thought to originate from cerebellar granule neuron progenitors (GNPs) that fail to undergo normal cell cycle exit and differentiation. Since microRNAs regulate numerous aspects of cellular physiology and development, we reasoned that alterations in miRNA expression might contribute to MB. We tested this hypothesis using two spontaneous mouse MB models with specific initiating mutations, Ink4c-/-; Ptch1+/- and Ink4c-/-; p53-/-. We found that 26 miRNAs showed increased expression and 24 miRNAs showed decreased expression in proliferating mouse GNPs and MBs relative to mature mouse cerebellum, regardless of genotype. Among the 26 overexpressed miRNAs, nine were encoded by the miR-17~92 cluster family, a group of microRNAs implicated as oncogenes in several tumor types. Analysis of human MBs demonstrated that three miR-17~92 cluster miRNAs (miR-92, miR-19a and miR-20) were also overexpressed in human MBs with a constitutively activated SHH signaling pathway, but not in other forms of the disease. To test whether the miR-17~92 cluster could promote MB formation, we enforced expression of these miRNAs in GNPs isolated from cerebella of postnatal (P) day P6 Ink4c-/-; Ptch1+/- mice. These, but not similarly engineered cells from Ink4c-/-; p53-/- mice, formed MBs in orthotopic transplants with complete penetrance. Interestingly, orthotopic mouse tumors ectopically expressing miR-17~92 lost expression of the wild-type Ptch1 allele. Our findings suggest a functional collaboration between the miR-17~92 cluster and the SHH signaling pathway in the development of MBs in mouse and man. Samples: purified CGNP-like mouse medulloblastoma cells; purified CGNPs from age day 6 (P6) mice; whole cerebellum from P6 mice; whole cerebellum from 1 month old mice. Each from three backgrounds (except tumors) - wt; Ptc+/-,Ink4c-/-; p53-/-,Ink4c-/-. Two to five biological replicates each.

Dataset Information

Gene expression data from postnatal day 7 subventricular zone (SVZ), IV ventricle and cerebellar white matter-derived neural stem cells (NSCs) and of cancer stem cells (CSCs) from Ptch het p53 wt and Ptch het p53 het mouse medulloblastomas

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