Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Neurosci Bull. 2019 Apr;35(2):216-224. doi: 10.1007/s12264-018-00329-6. Epub 2019 Jan 3.
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.
弥漫性内在脑桥神经胶质瘤(DIPG)是儿童脑瘤相关死亡的主要原因。到目前为止,这种疾病仍然缺乏有效的治疗方法,无法延长整体存活率。临床前癌症研究的一个典型策略是找出肿瘤组织与肿瘤旁正常组织之间的分子差异,以便确定潜在的治疗靶点。不幸的是,由于脑桥的重要功能,不可能获得 DIPG 的正常组织。在这里,我们报告了源自人胎儿后脑的神经祖细胞(脑桥祖细胞,PPCs)作为 DIPG 的正常对照细胞。PPCs 不仅具有与 DIPG 神经胶质瘤干细胞相似的细胞生物学和分子特征,而且还具有通过 DIPG 特异性突变 H3K27M 在体外永生化的潜力。这些发现为研究人员提供了候选的正常对照细胞和用于 DIPG 临床前研究的潜在药物载体。