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Effect of ZIC1 on group 3 medulloblastoma cell lines and granule neuron progenitor [ChIP-seq]

ABSTRACT: Investigate the DNA binding pattern as well as transcriptional consequences of ZIC1 and its medulloblastoma mutants in group 3 medulloblastoma cell lines and granule neuron progenitors

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE217638 | GEO | 2024/09/19

REPOSITORIES: GEO

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Effect of ZIC1 on group 3 medulloblastoma cell lines and granule neuron progenitor [RNA-seq]

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Effect of ZIC1 on group 3 medulloblastoma cell lines and granule neuron progenitor

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Effect of ZIC1 on group 3 medulloblastoma cell lines and granule neuron progenitor [RNA-seq]

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Acquisition of granule neuron precursor identity and Hedgehog-induced medulloblastoma in mice.

Project description:Origins of the brain tumor, medulloblastoma, from stem cells or restricted pro-genitor cells are unclear. To investigate this, we activated oncogenic Hedgehog signaling in multipotent and lineage-restricted CNS progenitors. We observed that normal unipo-tent cerebellar granule neuron precursors (CGNP) derive from hGFAP+ and Olig2+ rhombic lip progenitors. Hedgehog activation in a spectrum of early and late stage CNS progenitors generated similar medulloblastomas, but not other brain cancers, indicating that acquisition of CGNP identity is essential for tumorigenesis. We show in human and mouse medulloblastoma that cells expressing the glia-associated markers Gfap and Olig2 are neoplastic and that they retain features of embryonic-type granule lineage progenitors. Thus, oncogenic Hedgehog signaling promotes medulloblastoma from lineage-restricted granule cell progenitors. Gene expression profiling of cerebellar tumors generated from various early and late stage CNS progenitor cells.

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Project description:Sonic hedgehog (Shh) signals via Gli transcription factors to stimulate proliferation of granule neuron precursor cells (GNPs) in the cerebellum. Deregulation of Shh target genes often results in unrestrained GNP proliferation and eventually medulloblastoma (MB), the most common pediatric brain malignancy. Gene expression profiling was coupled with transcription factor binding location analysis to determine the Gli1-controlled transcriptional regulatory networks in GNPs and medulloblastoma cells. We detected significant overlap, as well as differences, in the Gli1-controlled transcriptional regulatory networks in GNPs and MBs. We determined the presence of gene expression in each dataset. There were 9260 genes expressed in Gli1-FLAG GNPs and 9185 genes expressed in Gli1-FLAG;Ptc+/- tumors; 8691 of which are in common. The large overlap is consistent with the cellular origin of these tumors. When the genes detectably expressed were intersected with our binding data, there were only 132 putative Gli1 target genes shared by both cell populations. Due to the heightened activation of the Hh pathway in tumors relative to GNPs, we further deduced direct Gli1 target genes exclusive to tumors by determining significantly induced genes in tumors versus in Ptc+/- GNPs. We identified at least 116 tumor-specific Gli1 target genes. These data suggest that tumor formation is accompanied by a tremendous change in the battery of Gli target genes. Presence of gene expression was determined for all samples: Gli1-FLAG-expressing GNPs, Ptc+/- GNPs, and Gli1-FLAG;Ptc+/-medulloblastomas. These datasets were intersected with chIP-chip data to determine potential direct Gli1 target genes. Differential gene expression was determined by comparing expression profiles from medulloblastoma tumors to those from Ptc+/- GNPs.

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Effect of ZIC1 on group 3 medulloblastoma cell lines and granule neuron progenitor

Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcription profiling of mouse with Hedgehog-induced medulloblastoma reveals oncogenic Hedgehog signaling promotes medulloblastoma from lineage-restricted granule cell progenitors

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