PDF(Pubmed)
Abstract：
Trophoblast stem cells (TSCs) can be chemically converted from embryonic stem cells (ESCs) in vitro. Although several transcription factors (TFs) have been recognized as essential for TSC formation, it remains unclear how differentiation cues link elimination of stemness with the establishment of TSC identity. Here, we show that PRDM14, a critical pluripotent circuitry component, is reduced during the formation of TSCs. The reduction is further shown to be due to the activation of Wnt/β-catenin signaling. The extinction of PRDM14 results in the erasure of H3K27me3 marks and chromatin opening in the gene loci of TSC TFs, including GATA3 and TFAP2C, which enables their expression and thus the initiation of the TSC formation process. Accordingly, PRDM14 reduction is proposed here as a critical event that couples elimination of stemness with the initiation of TSC formation. The present study provides novel insights into how induction signals initiate TSC formation.
摘要：
滋养层干细胞(TSC)可以在体外从胚胎干细胞(ESC)化学转化。虽然几种转录因子（TF）已被认为是TSC形成所必需的，目前尚不清楚分化线索如何将干性的消除与TSC身份的建立联系起来。这里,我们证明了PRDM14，一个关键的多能电路组件，在TSC形成期间减少。进一步显示该减少是由于Wnt/β-连环蛋白信号的激活。PRDM14的消失导致TSCTFs基因位点的H3K27me3标记和染色质开放的擦除，包括GATA3和TFAP2C，这使得它们能够表达，从而启动TSC形成过程。因此，这里提出PRDM14减少是将干性的消除与TSC形成的开始相关联的关键事件。本研究提供了有关感应信号如何引发TSC形成的新见解。
