School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, International Campus, Yonsei University, Incheon 21983, Korea.
Molecules. 2021 Sep 18;26(18):5665. doi: 10.3390/molecules26185665.
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 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 , 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.
在干细胞的细胞命运决定过程中会发生广泛的表观遗传重塑。此前，我们发现，桉脂素通过抑制信号分子来调节间充质干细胞的谱系承诺。然而，桉脂素处理在全基因组水平上的表观遗传调节尚未被分析。在这里，我们呈现了一个转录组谱分析数据，显示了桉脂素处理后 PRC2 靶基因的富集。此外，基因本体分析表明，桉脂素下调的 PRC2 靶基因与 Wnt 信号和多能性密切相关。我们选择 作为 Wnt 信号和多能性中桉脂素依赖的潜在顶级枢纽基因。通过 ChIP-qPCR 和 RT-qPCR，我们发现桉脂素处理增加了 PRC2 成分 EZH2 和 SUZ12 以及 H3K27me3 在 启动子区域的占有率，下调其转录水平。根据 GEO 图谱的分析，Oct4 耗竭的 DEGs 与桉脂素处理的 DEGs 呈现相反的模式。事实上，桉脂素处理后多能性标记物 Oct4、Sox2 和 Nanog 的表达上调。这一发现表明，桉脂素对 PRC2 动力学的药理学调节可能控制 Wnt 信号并维持干细胞的多能性。
