Extensive epigenetic remodeling occurs during the cell fate determination of stem cells. Previously, we discovered that eudesmin regulates lineage commitment of mesenchymal stem cells through the inhibition of signaling molecules. However, the epigenetic modulations upon eudesmin treatment in genomewide level have not been analyzed. Here, we present a transcriptome profiling data showing the enrichment in PRC2 target genes by eudesmin treatment. Furthermore, gene ontology analysis showed that PRC2 target genes downregulated by eudesmin are closely related to Wnt signaling and pluripotency. We selected DKK1 as an eudesmin-dependent potential top hub gene in the Wnt signaling and pluripotency. Through the ChIP-qPCR and RT-qPCR, we found that eudesmin treatment increased the occupancy of PRC2 components, EZH2 and SUZ12, and H3K27me3 level on the promoter region of DKK1, downregulating its transcription level. According to the analysis of GEO profiles, DEGs by depletion of Oct4 showed an opposite pattern to DEGs by eudesmin treatment. Indeed, the expression of pluripotency markers, Oct4, Sox2, and Nanog, was upregulated upon eudesmin treatment. This finding demonstrates that pharmacological modulation of PRC2 dynamics by eudesmin might control Wnt signaling and maintain pluripotency of stem cells.

中文翻译：

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基于转录组学的天然化合物 Eudesmin 作为 PRC2 调节剂的重新定位

在干细胞的细胞命运决定过程中发生了广泛的表观遗传重塑。以前，我们发现eudesmin 通过抑制信号分子来调节间充质干细胞的谱系定型。然而，尚未分析在全基因组水平上对eudesmin 治疗的表观遗传调节。在这里，我们提供了一个转录组分析数据，显示了通过eudesmin 处理对PRC2 靶基因的富集。此外，基因本体分析表明，被eudesmin下调的PRC2靶基因与Wnt信号传导和多能性密切相关。我们选择了DKK1作为 Wnt 信号传导和多能性中一种依赖于eudesmin 的潜在顶级中枢基因。通过ChIP-qPCR和RT-qPCR，我们发现eudesmin处理增加了DKK1启动子区PRC2组分、EZH2和SUZ12以及H3K27me3水平的占有率，下调了其转录水平。根据对 GEO 曲线的分析，Oct4 消耗的 DEG 显示出与 eudesmin 处理的 DEG 相反的模式。事实上，多能性标记物 Oct4、Sox2 和 Nanog 的表达在 eudesmin 处理后上调。这一发现表明，eudesmin 对 PRC2 动力学的药理学调节可能控制 Wnt 信号传导并维持干细胞的多能性。