When stimulated with a pulse from an exogenous WNT pathway activator, small aggregates of mouse embryonic stem cells (ESCs) can undergo embryo-like axial morphogenesis and patterning along the three major body axes. However, these structures, called gastruloids, currently lack the anterior embryonic regions, such as those belonging to the brain. Here we describe an approach to generate gastruloids that have a more complete antero-posterior development. We used bioengineered hydrogel microwell arrays to promote the robust derivation of mouse ESCs into post-implantation epiblast-like (EPI) aggregates in a reproducible and scalable manner. These EPI aggregates break symmetry and axially elongate without external chemical stimulation. Inhibition of WNT signaling in early stages of development leads to the formation of gastruloids with anterior neural tissues. Thus, we provide a new tool to study the development of the mouse after implantation in vitro, especially the formation of anterior neural regions.

中文翻译：

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在没有外源性Wnt激活的情况下产生的类胚体会发育前神经组织

当受到来自外源性WNT途径激活剂的脉冲刺激时，小鼠胚胎干细胞（ESC）的小聚集体会沿三个主要机体轴经历类似胚胎的轴向形态发生和构图。然而，这些被称为类胃泌体的结构目前缺乏前胚胎区域，例如那些属于大脑的区域。在这里，我们描述了一种产生具有更完整的前后发育的类固醇的方法。我们使用生物工程水凝胶微孔阵列，以可重现和可扩展的方式，促进了小鼠胚胎干细胞向植入后的成骨细胞样（EPI）聚集体的稳健衍生。这些EPI聚集体打破了对称性，并在没有外部化学刺激的情况下轴向伸长。WNT信号在发展的早期阶段的抑制导致与前神经组织的类胃激素的形成。因此，我们提供了一种新的工具来研究小鼠在体外植入后的发育，特别是前神经区域的形成。