Candidate pathways for promoting differentiation and quiescence of oligodendrocyte progenitor-like cells in glioblastoma. Mus musculus

The mature CNS contains PDGFRA+ ‘oligodendrocyte progenitor cells’ (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence. Overall design: There are two datasets here. One characterizes the normal translational profiles of neurons, astrocytes, mature and immature oligodendrocytes. Each cell type was profiled in triplicate, from pools of at least two mice, and total RNA controls were collected in parallel. The second dataset includes translational profiles of Olig2 positive cells from tumors form several variations of a murine model of glioma. Each variation was collected at least in triplicate, and total RNA controls were analyzed in parallel. All translational profiles were generated using the Translating Ribosome Affinity Purification protocol.

成熟中枢神经系统（CNS）中存在血小板衍生生长因子受体α阳性（PDGFRA+）的少突胶质细胞前体细胞（oligodendrocyte progenitor cells, OPC），这类细胞可处于静息状态、增殖或分化为少突胶质细胞。在人类神经胶质瘤中，常可观察到表型与OPCs相似、增殖活跃的Olig2+细胞。本研究旨在体内筛选出仅对OPC分化或静息状态维持必需的候选通路。

我们借助bacTRAP技术，构建并分析了可用于正常小鼠脑内主要细胞类型（包括OPCs）翻译组谱分析的小鼠品系。随后，我们对血小板衍生生长因子驱动的小鼠神经胶质瘤模型中的少突胶质细胞谱系（Olig2+）细胞进行了翻译组谱分析。该分析证实，Olig2+肿瘤细胞与OPCs的相似性最高，但同时也鉴定出了关键前体细胞基因的表达差异——这些差异基因可作为促进细胞分化或维持静息状态的候选靶点。

总体设计：本研究包含两个数据集。第一个数据集用于表征神经元、星形胶质细胞、成熟及未成熟少突胶质细胞的正常翻译组谱。每种细胞类型均设置三次生物学重复，样本取自至少两只小鼠的混合组织，同时平行收集总RNA对照样本。第二个数据集则包含来自多种小鼠神经胶质瘤模型变体的肿瘤组织中Olig2阳性细胞的翻译组谱。每种模型变体均设置至少三次生物学重复，同时平行分析总RNA对照样本。所有翻译组谱分析均采用翻译核糖体亲和纯化（Translating Ribosome Affinity Purification）方案完成。