Adult oligodendrocyte progenitors (aOPCs) generate myelinating oligodendrocytes like neonatal progenitors (nOPCs), and they also display unique functional features. Here, using unbiased histone proteomics analysis and ChIP sequencing analysis of PDGFRα+ OPCs sorted from neonatal and adult Pdgfra-H2B-EGFP reporter mice, we identify the activating H4K8ac histone mark as enriched in the aOPCs. We detect increased occupancy of the H4K8ac activating mark at chromatin locations corresponding to genes related to the progenitor state (e.g., Hes5, Gpr17), metabolic processes (e.g., Txnip, Ptdgs), and myelin components (e.g., Cnp, Mog). aOPCs showed higher levels of transcripts related to lipid metabolism and myelin, and lower levels of transcripts related to cell cycle and proliferation compared with nOPCs. In addition, pharmacological inhibition of histone acetylation decreased the expression of the H4K8ac target genes in aOPCs and decreased their proliferation. Overall, this study identifies acetylation of the histone H4K8 as a regulator of the proliferative capacity of aOPCs.

中文翻译：

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组蛋白 H4 乙酰化差异调节成年少突胶质细胞祖细胞的增殖。


成人少突胶质细胞祖细胞（aOPC）像新生儿祖细胞（nOPC）一样产生髓鞘少突胶质细胞，并且它们还表现出独特的功能特征。在这里，利用对从新生和成年 Pdgfra-H2B-EGFP 报告小鼠中分选的 PDGFRα+ OPC 的无偏组蛋白组蛋白组学分析和 ChIP 测序分析，我们确定了 aOPC 中富集的激活 H4K8ac 组蛋白标记。我们检测到与祖细胞状态（例如，Hes5、Gpr17）、代谢过程（例如，Txnip、Ptdgs）和髓磷脂成分（例如，Cnp、Mog）相关的基因相对应的染色质位置上H4K8ac激活标记的占据增加。与 nOPC 相比，aOPC 与脂质代谢和髓磷脂相关的转录物水平较高，而与细胞周期和增殖相关的转录物水平较低。此外，组蛋白乙酰化的药理抑制会降低 aOPC 中 H4K8ac 靶基因的表达，并减少其增殖。总体而言，本研究确定组蛋白 H4K8 的乙酰化是 aOPC 增殖能力的调节因子。