Diffuse Intrinsic Pontine Gliomas Exhibit Cell Biological and Molecular Signatures of Fetal Hindbrain-Derived Neural Progenitor Cells
Yu Sun1 • Cheng Xu1 • Changcun Pan1 • Xin Chen1 • Yibo Geng1 • Yuliang Wu1 • Peng Zhang1 • Wenhao Wu1 • Yu Wang1 • Deling Li1 • Zhen Wu1 • Junting Zhang1 • Qiaoran Xi2 • Liwei Zhang1,*
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
2Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG. The PPCs not only harbored similar cell biological and molecular signatures as DIPG glioma stem cells, but also had the potential to be immortalized by the DIPG-specific mutation H3K27M in vitro. These findings provide researchers with a candidate normal control and a potential medicine carrier for preclinical research on DIPG.
Diffuse intrinsic pontine glioma; Neural progenitor cells; Immortalization; H3K27M; Senescence