학술논문

Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells.
Document Type
Article
Source
Proceedings of the National Academy of Sciences of the United States of America. 8/18/2020, Vol. 117 Issue 33, p20127-20138. 12p.
Subject
*NEURAL stem cells
*MEDULLOBLASTOMA
*BASAL cell nevus syndrome
*TUMORS in children
*CEREBELLAR tumors
Language
ISSN
0027-8424
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. [ABSTRACT FROM AUTHOR]