Abstract:
Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-β, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.
摘要:
胚胎发生需要胚胎和胚外组织之间的和谐协调。尽管已经产生了胚胎和胚胎外来源的干细胞,它们生长在不同的文化条件下。在这项研究中,利用激活FGF的统一培养条件,TGF-β,和WNT途径,我们已经成功地获得了胚胎干细胞(FTW-ESC),胚外内胚层干细胞(FTW-XENs),和来自小鼠和食蟹猴(猕猴)胚泡的三个基础组织的滋养层干细胞(FTW-TSC)。这种方法促进了胚胎和胚外干细胞的共培养,揭示了胚外内胚层细胞对多能细胞的生长抑制作用,部分通过细胞外基质信号传导。此外,我们的跨物种分析确定了调节FTW-XEN的共有和独特的转录因子和途径。胚胎和胚胎外干细胞共培养策略为开发更忠实的胚胎模型和设计更多与发育相关的分化方案提供了有希望的途径。