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

Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20127-20138. doi: 10.1073/pnas.1920521117. Epub 2020 Aug 3.


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.

Keywords: disease model; medulloblastoma; neural stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology
  • Animals
  • Basal Cell Nevus Syndrome / genetics
  • Basal Cell Nevus Syndrome / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Galectin 1 / genetics
  • Galectin 1 / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Medulloblastoma / genetics*
  • Mice
  • Neoplasms, Experimental
  • Neural Stem Cells / physiology*
  • Patched-1 Receptor / genetics
  • Pyridines / pharmacology


  • Anilides
  • Galectin 1
  • Hedgehog Proteins
  • HhAntag691
  • PTCH1 protein, human
  • Patched-1 Receptor
  • Pyridines
  • SHH protein, human