The emergence of germ layers in embryos during gastrulation is a key developmental milestone. How morphogenetic signals engage the regulatory networks responsible for early embryonic tissue patterning is incompletely understood. To understand this, we developed a gene regulatory network (GRN) model of human pluripotent stem cell (hPSC) lineage commitment and embedded it into cellular agents that respond to a dynamic signalling microenvironment. We found that cellular pattern order, composition, and dynamics were predictably manipulable based on the GRN wiring. We showed that feedback between OCT4, and BMP and WNT pathways created a dynamic OCT4 front that mediates the spatiotemporal evolution of developmental patterns. Translocation of this radial front can be predictively disrupted in vitro to control germ-layer pattern composition. This work links the emergence of multicellular patterns to regulatory network activity in individual hPSCs. We anticipate our approach will help to understand how GRN structure regulates organogenesis in different contexts.

中文翻译：

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基因调节网络（GRN）嵌入剂将细胞决策与人多能干细胞衍生的细菌层样模式形成联系起来

胚芽过程中胚层中胚层的出现是一个重要的发展里程碑。形态发生信号如何参与负责早期胚胎组织模式的调节网络尚未完全了解。为了理解这一点，我们开发了人类多能干细胞（hPSC）谱系承诺的基因调控网络（GRN）模型，并将其嵌入对动态信号微环境有反应的细胞因子中。我们发现，基于GRN布线，可预测地可操纵细胞模式的顺序，组成和动力学。我们表明，OCT4与BMP和WNT途径之间的反馈创建了一个动态的OCT4前沿，该前沿介导了发展模式的时空演化。可以预测性地破坏此径向前部的移位，以控制胚芽模式组成。这项工作将多细胞模式的出现与单个hPSC中的调节网络活动联系起来。我们预期我们的方法将有助于理解GRN结构如何在不同情况下调节器官发生。