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  • Huang, MillerUniv Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)

Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • CELL PRESS,2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-394687
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-394687URI
  • https://doi.org/10.1016/j.stem.2019.05.013DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 predis- posed 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Tailor, JigneshUniv Cambridge, MRC Stem Cell Inst, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QR, England;Inst Canc Res, London SM2 5NG, England;Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada;Hosp Sick Children, Div Neurosurg, Toronto, ON, Canada (author)
  • Zhen, QiqiUniv Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)
  • Gillmor, Aaron H.Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada;Univ Calgary, Charbonneau Canc Inst, Calgary, AB, Canada;Alberta Childrens Prov Gen Hosp, Res Inst, Calgary, AB, Canada (author)
  • Miller, Matthew L.Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)
  • Weishaupt, HolgerUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)holwe849 (author)
  • Chen, JustinStanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA (author)
  • Zheng, TinaUniv Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)
  • Nash, Emily K.Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)
  • McHenry, Lauren K.Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)
  • An, ZhenyiUniv Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)
  • Ye, FubaiyangUniv Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)
  • Takashima, YasuhiroUniv Cambridge, MRC Stem Cell Inst, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QR, England (author)
  • Clarke, JamesUniv Cambridge, MRC Stem Cell Inst, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QR, England (author)
  • Ayetey, HaroldUniv Cambridge, MRC Stem Cell Inst, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QR, England (author)
  • Cavalli, Florence MgHosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada;Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada (author)
  • Luu, BettyHosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada;Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada (author)
  • Moriarity, Branden S.Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA;Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA;Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA (author)
  • Ilkhanizadeh, ShirinUniv Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA (author)
  • Chavez, LukasHopp Childrens Canc Ctr KiTZ, Heidelberg, Germany;German Canc Consortium DKTK, Div Pediat Neurooncol, German Canc Res Ctr DKFZ, Heidelberg, Germany (author)
  • Yu, ChunyingHosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada (author)
  • Kurian, Kathreena M.Univ Bristol, Southmead Hosp, Inst Clin Neurosci, Level 1,Learning & Res Bldg, Bristol BS10 5NB, Avon, England (author)
  • Magnaldo, ThierryNice UMR CNRS 7284 INSERM U1081 UNS UCA, Inst Res Canc & Aging, Nice, France (author)
  • Sevenet, NicolasUniv Bordeaux, Inst Bergonie, 229 Cours Argonne, F-33076 Bordeaux, France;Univ Bordeaux, INSERM U1218, 229 Cours Argonne, F-33076 Bordeaux, France (author)
  • Koch, PhilippHeidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Mannheim, Germany;Hector Inst Translat Brain Res HITBR gGmbH, Mannheim, Germany;German Canc Res Ctr, Heidelberg, Germany (author)
  • Pollard, Steven M.Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Canc Res UK Edinburgh Ctr, Edinburgh, Midlothian, Scotland (author)
  • Dirks, PeterHosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada;Hosp Sick Children, Div Neurosurg, Toronto, ON, Canada;Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada (author)
  • Snyder, Michael P.Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA (author)
  • Largaespada, David A.Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA;Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA;Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA (author)
  • Cho, Yoon JaeOregon Hlth & Sci Univ, Dept Pediat, Div Pediat Neurol, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA;Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA;Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA (author)
  • Phillips, Joanna J.Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94158 USA;Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94158 USA (author)
  • Johansson Swartling, Fredrik,1975-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)fredjoha (author)
  • Morrissy, A. SoranaHosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada;Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada;Univ Calgary, Charbonneau Canc Inst, Calgary, AB, Canada;Alberta Childrens Prov Gen Hosp, Res Inst, Calgary, AB, Canada;Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada (author)
  • Kool, MarcelHopp Childrens Canc Ctr KiTZ, Heidelberg, Germany;German Canc Consortium DKTK, Div Pediat Neurooncol, German Canc Res Ctr DKFZ, Heidelberg, Germany (author)
  • Pfister, Stefan M.Hopp Childrens Canc Ctr KiTZ, Heidelberg, Germany;German Canc Consortium DKTK, Div Pediat Neurooncol, German Canc Res Ctr DKFZ, Heidelberg, Germany;Heidelberg Univ Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany (author)
  • Taylor, Michael D.Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada;Hosp Sick Children, Div Neurosurg, Toronto, ON, Canada;Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada;Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada (author)
  • Smith, AustinUniv Cambridge, MRC Stem Cell Inst, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QR, England (author)
  • Weiss, William A.Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA;Univ Calif San Francisco, Res Ctr, Dept Pediat, San Francisco, CA 94158 USA;Univ Calif San Francisco, Res Ctr, Dept Neurosurg, San Francisco, CA 94158 USA;Univ Calif San Francisco, Res Ctr, Dept Brain Tumor, San Francisco, CA 94158 USA (author)
  • Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA;Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USAUniv Cambridge, MRC Stem Cell Inst, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QR, England;Inst Canc Res, London SM2 5NG, England;Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada;Hosp Sick Children, Div Neurosurg, Toronto, ON, Canada (creator_code:org_t)

Related titles

  • In:Cell Stem Cell: CELL PRESS25:3, s. 433-+1934-59091875-9777

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