Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells

Research output: Contribution to journalArticle


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.


  • Evelyn Susanto
  • Ana Marin Navarro
  • Leilei Zhou
  • Anders Sundström
  • Niek van Bree
  • Marina Stantic
  • Mohsen Moslem
  • Jignesh Tailor
  • Jonne Rietdijk
  • Veronica Zubillaga
  • Jens Martin Hübner
  • Holger Weishaupt
  • Johanna Wolfsberger
  • Irina Alafuzoff
  • Ann Nordgren
  • Thierry Magnaldo
  • John Inge Johnsen
  • Marcel Kool
  • Kristiina Tammimies
  • Fredrik J. Swartling
  • Anna Falk
  • Margareta Wilhelm
External organisations
  • Karolinska Institutet
  • Uppsala University
  • Hospital for Sick Children, Toronto
  • University of Toronto
  • German Cancer Research Centre
  • Karolinska University Hospital
  • Skåne University Hospital
  • Université Nice Sophia Antipolis
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Cancer and Oncology


  • disease model, medulloblastoma, neural stem cells
Original languageEnglish
Pages (from-to)20127-20138
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number33
Publication statusPublished - 2020
Publication categoryResearch