原神经胶质瘤是一种脑肿瘤，其特征是少突胶质细胞祖细胞（OPC）转录物的富集和遗传改变。在这项研究中，我们试图鉴定具有Trp53缺失和PDGF-BB过表达（BB-p53n）的OPC之间的转录和表观遗传差异，这些OPC在移植到小鼠大脑中时会形成肿瘤，而那些仅携带p53缺失（p53n）的OPC则不会。我们对这两个转基因 OPC 群体进行了无偏的组蛋白蛋白质组学和 RNA-seq 分析，并检测到与 p53n OPC 相比，BB-p53n 中 H3K27me3 的水平更高。 BB-p53n OPC 的特点是与增殖相关的转录物水平较高，而与分化相关的转录物水平较低。 BB-p53n OPC 中组蛋白 H3K27 三甲基化的药理学抑制可减少细胞周期转录并增加分化标记物的表达。这些数据表明，p53 null OPC 中的 PDGF-BB 过表达会导致组蛋白翻译后修饰和随后的转录变化，有利于增殖，同时停止分化，从而促进转化的早期阶段。

Proneural gliomas are brain tumors characterized by enrichment of oligodendrocyte progenitor cell (OPC) transcripts and genetic alterations. In this study we sought to identify transcriptional and epigenetic differences between OPCs with Trp53 deletion and PDGF-BB overexpression (BB-p53n), which form tumors when transplanted in mouse brains, and those carrying only p53 deletion (p53n), which do not. We used unbiased histone proteomics and RNA-seq analysis on these two genetically modified OPC populations and detected higher levels of H3K27me3 in BB-p53n compared to p53n OPCs. The BB-p53n OPC were characterized by higher levels of transcripts related to proliferation and lower levels of those related to differentiation. Pharmacological inhibition of histone H3K27 trimethylation in BB-p53n OPC reduced cell cycle transcripts and increased the expression of differentiation markers. These data suggest that PDGF-BB overexpression in p53 null OPC results in histone post-translational modifications and consequent transcriptional changes favoring proliferation while halting differentiation, thereby promoting the early stages of transformation.