The human blastocyst contains the pluripotent epiblast from which human embryonic stem cells (hESCs) can be derived. ACTIVIN/NODAL signaling maintains expression of the transcription factor NANOG and in vitro propagation of hESCs. It is unknown whether this reflects a functional requirement for epiblast development in human embryos. Here, we characterized NODAL signaling activity during pre-implantation human development. We showed that NANOG is an early molecular marker restricted to the nascent human pluripotent epiblast and was initiated prior to the onset of NODAL signaling. We further demonstrated that expression of pluripotency-associated transcription factors NANOG, SOX2, OCT4, and KLF17 were maintained in the epiblast in the absence of NODAL signaling activity. Genome-wide transcriptional analysis showed that NODAL signaling inhibition did not decrease NANOG transcription or impact the wider pluripotency-associated gene regulatory network. These data suggest differences in the signaling requirements regulating pluripotency in the pre-implantation human epiblast compared with existing hESC culture.

中文翻译：

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在植入前人类发育中多能上胚层的启动和维持与 NODAL 信号转导无关


人囊胚包含多能上皮细胞，人胚胎干细胞 （hESC） 可从中衍生。ACTIVIN/NODAL 信号转导维持转录因子 NANOG 的表达和 hESC 的体外繁殖。目前尚不清楚这是否反映了人类胚胎中上胚层发育的功能要求。在这里，我们表征了植入前人类发育过程中的 NODAL 信号活性。我们表明 NANOG 是一种早期分子标志物，仅限于新生的人类多能上皮细胞，并且在 NODAL 信号传导开始之前启动。我们进一步证明，在没有 NODAL 信号活性的情况下，多能性相关转录因子 NANOG 、 SOX2 、 OCT4 和 KLF17 的表达在上胚层中得维持。全基因组转录分析表明，NODAL 信号抑制不会降低 NANOG 转录或影响更广泛的多能性相关基因调控网络。这些数据表明，与现有的 hESC 培养物相比，植入前人上胚层细胞调节多能性的信号传导要求存在差异。