Polycomb group (PcG) RING finger protein 5 (PCGF5) is a core component of the so-called Polycomb repressive complex 1.5 (PRC1.5), which is involved in epigenetic transcriptional repression. To explore the developmental function of Pcgf5, we generated Pcgf5 knockout (Pcgf5-/- ) mouse embryonic stem cell (mESC) lines with the help of CRISPR/Cas9 technology. We subjected the Pcgf5-/- and wild-type (WT) mESCs to a differentiation protocol toward mesodermal-cardiac cell types as aggregated embryoid bodies (EBs) and we found that knockout of Pcgf5 delayed the generation of the three germ layers, especially the ectoderm. Further, disruption of Pcgf5 impacted the epithelial-mesenchymal transition during EB morphogenesis and differentially affected the gene expression of essential developmental signaling pathways such as Nodal and Wnt. Finally, we also unveiled that loss of Pcgf5 induced the repression of genes involved in the Notch pathway, which may explain the enhancement of cardiomyocyte maturation and the dampening of ectodermal-neural differentiation observed in the Pcgf5-/- EBs.

中文翻译：

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在小鼠胚胎干细胞的体外分化过程中，Polycomb组的RING指蛋白5影响了几个发育信号通路。

Polycomb group（PcG）RING指蛋白5（PCGF5）是所谓的Polycomb Repressive Complex 1.5（PRC1.5）的核心成分，它参与表观遗传转录抑制。为了探索Pcgf5的发育功能，我们借助CRISPR / Cas9技术生成了Pcgf5敲除（Pcgf5-/-）小鼠胚胎干细胞（mESC）系。我们对Pcgf5-/-和野生型（WT）mESC进行了针对中胚层心脏细胞类型的分化协议，即聚集的胚状体（EBs），我们发现Pcgf5的敲除延迟了三个胚层的产生，特别是外胚层。此外，Pcgf5的破坏会影响EB形态发生过程中的上皮-间质转化，并差异性地影响诸如Nodal和Wnt等基本发育信号通路的基因表达。最后，