Abstract：
Mechanisms controlling trophoblast proliferation and differentiation during embryo implantation are poorly understood. Human trophoblast stem cells (TSC) and BMP4/A83-01/PD173074-treated pluripotent stem cell-derived trophoblast cells (BAP) are two widely employed, contemporary models to study trophoblast development and function, but how faithfully they mimic early trophoblast cells has not been fully examined. We evaluated the transcriptomes of trophoblast cells from BAP and TSC and directly compared them with those from peri-implantation human embryos during extended embryo culture (EEC) between embryonic day 8 to 12. The BAP and TSC grouped closely with trophoblast cells from EEC within each trophoblast sublineage following dimensional analysis and unsupervised hierarchical clustering. However, subtle differences in transcriptional programs existed within each trophoblast sublineage. We also validated the presence of six genes in peri-implantation human embryos by immunolocalization. Our analysis reveals that both BAP and TSC models have features of peri-implantation trophoblasts, while maintaining minor transcriptomic differences, and thus serve as valuable tools for studying implantation in lieu of human embryos.
摘要：
在胚胎植入过程中控制滋养层增殖和分化的机制知之甚少。人滋养层干细胞（TSC）和BMP4/A83-01/PD173074处理的多能干细胞来源的滋养层细胞（BAP）是两种广泛使用的细胞，研究滋养细胞发育和功能的当代模型，但是它们如何忠实地模仿早期滋养层细胞还没有得到充分的研究。我们评估了来自BAP和TSC的滋养层细胞的转录组，并在胚胎第8天至第12天之间的扩展胚胎培养（EEC）期间将其与来自着床人胚胎的转录组直接进行比较。在维度分析和无监督分层聚类之后，BAP和TSC与每个滋养层亚谱系中来自EEC的滋养层细胞紧密分组。然而,每个滋养层亚谱系中的转录程序存在细微差异。我们还通过免疫定位验证了人胚胎中六个基因的存在。我们的分析表明，BAP和TSC模型都具有围植入滋养细胞的特征，同时保持微小的转录组差异，因此，作为研究植入代替人类胚胎的有价值的工具。
