Bérenger-Currias Noémie Mlp, Mircea Maria, Adegeest Esmée, van den Berg Patrick R, Feliksik Marleen, Hochane Mazène, Idema Timon, Tans Sander J, Semrau Stefan
Department of Physics, Leiden University, Leiden, The Netherlands.
Delft University of Technology, Department of Bionanoscience, Kavli Institute of Nanoscience, Delft, The Netherlands.
J Tissue Eng. 2022 Jun 11;13:20417314221103042. doi: 10.1177/20417314221103042. eCollection 2022 Jan-Dec.
Stem-cell derived in vitro systems, such as organoids or embryoids, hold great potential for modeling in vivo development. Full control over their initial composition, scalability, and easily measurable dynamics make those systems useful for studying specific developmental processes in isolation. Here we report the formation of gastruloids consisting of mouse embryonic stem cells (mESCs) and extraembryonic endoderm (XEN) cells. These XEN-enhanced gastruloids (XEGs) exhibit the formation of neural epithelia, which are absent in gastruloids derived from mESCs only. By single-cell RNA-seq, imaging, and differentiation experiments, we demonstrate the neural characteristics of the epithelial tissue. We further show that the mESCs induce the differentiation of the XEN cells to a visceral endoderm-like state. Finally, we demonstrate that local inhibition of WNT signaling and production of a basement membrane by the XEN cells underlie the formation of the neuroepithelial tissue. In summary, we establish XEGs to explore heterotypic cellular interactions and their developmental consequences in vitro.
源自干细胞的体外系统，如类器官或类胚体，在模拟体内发育方面具有巨大潜力。对其初始组成、可扩展性以及易于测量的动态过程的完全控制，使得这些系统可用于单独研究特定的发育过程。在此，我们报告了由小鼠胚胎干细胞（mESC）和胚外内胚层（XEN）细胞组成的原肠胚样结构的形成。这些XEN增强型原肠胚样结构（XEG）表现出神经上皮的形成，而仅由mESC衍生的原肠胚样结构中不存在这种情况。通过单细胞RNA测序、成像和分化实验，我们证明了上皮组织的神经特征。我们进一步表明，mESC诱导XEN细胞分化为内脏内胚层样状态。最后，我们证明XEN细胞对WNT信号的局部抑制和基底膜的产生是神经上皮组织形成的基础。总之，我们建立了XEG来探索体外异型细胞间相互作用及其发育后果。
