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000144001 0247_ $$2doi$$a10.1016/j.stem.2019.05.013
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000144001 1001_ $$aHuang, Miller$$b0
000144001 245__ $$aEngineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis.
000144001 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2019
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000144001 520__ $$aHuman neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predisposed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.
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000144001 7001_ $$aTailor, Jignesh$$b1
000144001 7001_ $$aZhen, Qiqi$$b2
000144001 7001_ $$aGillmor, Aaron H$$b3
000144001 7001_ $$aMiller, Matthew L$$b4
000144001 7001_ $$aWeishaupt, Holger$$b5
000144001 7001_ $$aChen, Justin$$b6
000144001 7001_ $$aZheng, Tina$$b7
000144001 7001_ $$aNash, Emily K$$b8
000144001 7001_ $$aMcHenry, Lauren K$$b9
000144001 7001_ $$aAn, Zhenyi$$b10
000144001 7001_ $$aYe, Fubaiyang$$b11
000144001 7001_ $$aTakashima, Yasuhiro$$b12
000144001 7001_ $$aClarke, James$$b13
000144001 7001_ $$aAyetey, Harold$$b14
000144001 7001_ $$aCavalli, Florence M G$$b15
000144001 7001_ $$aLuu, Betty$$b16
000144001 7001_ $$aMoriarity, Branden S$$b17
000144001 7001_ $$aIlkhanizadeh, Shirin$$b18
000144001 7001_ $$0P:(DE-He78)082dd3179733e3e716a58eb90f418a78$$aChavez, Lukas$$b19$$udkfz
000144001 7001_ $$aYu, Chunying$$b20
000144001 7001_ $$aKurian, Kathreena M$$b21
000144001 7001_ $$aMagnaldo, Thierry$$b22
000144001 7001_ $$aSevenet, Nicolas$$b23
000144001 7001_ $$0P:(DE-HGF)0$$aKoch, Philipp$$b24
000144001 7001_ $$aPollard, Steven M$$b25
000144001 7001_ $$aDirks, Peter$$b26
000144001 7001_ $$aSnyder, Michael P$$b27
000144001 7001_ $$aLargaespada, David A$$b28
000144001 7001_ $$aCho, Yoon Jae$$b29
000144001 7001_ $$aPhillips, Joanna J$$b30
000144001 7001_ $$aSwartling, Fredrik J$$b31
000144001 7001_ $$aMorrissy, A Sorana$$b32
000144001 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b33$$udkfz
000144001 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b34$$udkfz
000144001 7001_ $$aTaylor, Michael D$$b35
000144001 7001_ $$aSmith, Austin$$b36
000144001 7001_ $$aWeiss, William A$$b37
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