Supporting data for “TP53 is required for trophoblast lineage development from human expanded potential stem cells”

This dataset covers the major findings of the investigation of p53 functions in human trophoblast development. In this dataset, it is presented that heterogenous expression of p53 in human expanded stem cells (EPSCs) is associated with cell cycle state and trophoblast differentiation potential. By generating p53-null human EPSCs, it was demonstrated that p53 deficiency compromised trophoblast differentiation and impaired trophoblast functions including the ability to secret pregnancy-associated hormone and the ability to implant. Transcriptomic analysis suggested hyperactivation of ERK/MAPK signaling upon loss of p53, and inhibition of ERK proteins restored the trophoblast differentiation potential from p53-null human EPSCs. Furthermore, in the established human trophoblast stem cells (TSCs), loss of p53 altered global chromatin accessibility, regions of which were enriched for motifs for trophoblast master regulators. As a consequence, p53-null human TSCs exhibited compromised differentiation potential into trophoblast sub-lineages. More importantly, in vivo mouse early pre-implantation embryonic model further underscored the importance of p53 in trophectoderm lineage development. The study present here has uncovered a novel role of p53 in human trophoblast development and carries novel insights for clinical applications.

本数据集涵盖了关于人类滋养层发育中p53功能研究的主要发现。在该数据集中，阐述了人类扩展干细胞（EPSCs）中p53的异质性表达与细胞周期状态及滋养层分化潜能的相关性。通过构建p53敲除型人类EPSCs，本研究证实了p53的缺乏损害了滋养层的分化，并干扰了滋养层的多种功能，包括分泌妊娠相关激素的能力和植入能力。转录组分析揭示了p53缺失后ERK/MAPK信号通路的过度激活，以及ERK蛋白的抑制能够恢复p53敲除型人类EPSCs的滋养层分化潜能。此外，在已建立的滋养层干细胞（TSCs）中，p53的缺失改变了全球染色质可及性，其中富含滋养层关键调控因子模式的区域。因此，p53敲除型人类TSCs表现出向滋养层亚型分化的受损潜能。更重要的是，通过体内小鼠早期预植入胚胎模型进一步强调了p53在滋养层谱系发育中的重要性。本研究揭示了p53在人类滋养层发育中的新颖作用，并为临床应用提供了新的洞见。