Journal Article

DKFZ-2020-01601

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells.

Susanto, E. ; Marin Navarro, A. ; Zhou, L. ; Sundström, A. ; van Bree, N. ; Stantic, M. ; Moslem, M. ; Tailor, J. ; Rietdijk, J. ; Zubillaga, V. ; Hübner, J.-M.DKFZ* ; Weishaupt, H. ; Wolfsberger, J. ; Alafuzoff, I. ; Nordgren, A. ; Magnaldo, T. ; Siesjö, P. ; Johnsen, J. I. ; Kool, M.DKFZ* ; Tammimies, K. ; Darabi, A. ; Swartling, F. J. ; Falk, A. ; Wilhelm, M.

2020
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1920521117

Abstract: Medulloblastoma is the most common malignant brain tumor in children. Here we describe a medulloblastoma model using Induced pluripotent stem (iPS) cell-derived human neuroepithelial stem (NES) cells generated from a Gorlin syndrome patient carrying a germline mutation in the sonic hedgehog (SHH) receptor PTCH1. We found that Gorlin NES cells formed tumors in mouse cerebellum mimicking human medulloblastoma. Retransplantation of tumor-isolated NES (tNES) cells resulted in accelerated tumor formation, cells with reduced growth factor dependency, enhanced neurosphere formation in vitro, and increased sensitivity to Vismodegib. Using our model, we identified LGALS1 to be a GLI target gene that is up-regulated in both Gorlin tNES cells and SHH-subgroup of medulloblastoma patients. Taken together, we demonstrate that NES cells derived from Gorlin patients can be used as a resource to model medulloblastoma initiation and progression and to identify putative targets.

Note: 2020 Aug 18;117(33):20127-20138

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2020

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; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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