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Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis.

Cell Stem Cell. 2019-06; 
HuangMiller,TailorJignesh,ZhenQiqi,GillmorAaron H,MillerMatthew L,WeishauptHolger,ChenJustin,ZhengTina,NashEmily K,McHenryLauren K,AnZhenyi,YeFubaiyang,TakashimaYasuhiro,ClarkeJames,AyeteyHarold,CavalliFlorence M G,LuuBetty,MoriarityBranden S,IlkhanizadehShirin,ChavezLukas,YuChunying,KurianKathreena M,MagnaldoThierry,SevenetNicolas,KochPhilipp,PollardSteven M,DirksPeter,SnyderMichael P,LargaespadaDavid A,ChoYoon Jae,PhillipsJoanna J,SwartlingFredrik J,MorrissyA Sorana,KoolMarcel,PfisterStefan M,TaylorMichael D,SmithAustin,WeissWilli
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摘要

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 syndrom... More

關鍵詞

SHH,human pluripotent stem cells,medulloblastoma,neuroepithelial stem c
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