Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland; Institute of Chemical Sciences and Engineering, School of Basic Science, EPFL, 1015 Lausanne, Switzerland.
Stem Cell Reports. 2021 May 11;16(5):1143-1155. doi: 10.1016/j.stemcr.2021.03.017. Epub 2021 Apr 22.
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 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.
当受到外源性 WNT 途径激活剂脉冲的刺激时，小鼠胚胎干细胞 (ESC) 的小聚集体可以进行胚胎样轴向形态发生，并沿着三个主要的体轴进行模式形成。然而，这些被称为胚状体的结构目前缺乏前胚胎区域，例如属于大脑的区域。在这里，我们描述了一种生成具有更完整前后发育的胚状体的方法。我们使用水凝胶微井阵列以可重复和可扩展的方式促进小鼠 ESC 大量生成植入后类内胚层 (EPI) 聚集体。这些 EPI 聚集体打破对称性并轴向伸长，而无需外部化学刺激。在发育的早期阶段抑制 WNT 信号会导致形成具有前神经组织的胚状体。因此，我们提供了一种新的工具来研究体外植入后的小鼠发育，特别是前神经区域的形成。
