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Directed differentiation of human hindbrain neuroepithelial stem cells recapitulates cerebellar granule neurogenesis.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE233339 | GEO | 2023/05/29

REPOSITORIES: GEO

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Directed differentiation of human hindbrain neuroepithelial stem cells recapitulates cerebellar granule neurogenesis [scRNA-seq]

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Directed differentiation of human hindbrain neuroepithelial stem cells recapitulates cerebellar granule neurogenesis.

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Project description:Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predisposed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.

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The Chromatin Remodelling Contributions of Snf2l in Cerebellar Granule Neuron Differentiation

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

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Inferring Regulatory Programs Governing Region Specificity of Neuroepithelial Stem Cells during Early Hindbrain and Spinal Cord Development.

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