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Abstract：
The spatial sorting of cells into appropriate tissue compartments is essential for embryogenesis and tissue development. Spatial cell sorting is controlled by the interplay between cell surface affinity and intracellular mechanical properties. However, intracellular signaling that can sufficiently sort cell populations remains unexplored. In this study, we engineered chimeric cadherins by replacing the cadherin intracellular domain with cytoskeletal regulators to test their ability to induce spatial cell sorting. Using a fibroblast-based reconstitution system, we observed that Rac1 and RhoA activity in the cadherin tail induced outward and inward sorting, respectively. In particular, RhoA activity embedded cells toward the inside of E-cadherin-expressing spheroids and tumor spheroids, leading to tissue invagination. Despite the simplicity of chimeric cadherin design, our results indicate that differences in cadherin intracellular activities can determine the direction of spatial cell sorting, even when cell surface affinity is not different, and provide new molecular tools to engineer tissue architectures.
摘要：
将细胞空间分选到适当的组织区室中对于胚胎发生和组织发育至关重要。空间细胞分选由细胞表面亲和力和细胞内机械性质之间的相互作用控制。然而,可以充分分选细胞群体的细胞内信号仍未被探索。在这项研究中,我们通过用细胞骨架调节因子替换钙粘蛋白胞内结构域来设计嵌合钙粘蛋白，以测试它们诱导空间细胞分选的能力。使用基于成纤维细胞的重建系统，我们观察到钙黏着蛋白尾部的Rac1和RhoA活性诱导了向外和向内的分选，分别。特别是,RhoA活性嵌入细胞朝向E-cadherin表达球体和肿瘤球体的内部，导致组织内陷。尽管嵌合钙粘蛋白设计简单，我们的结果表明，钙黏着蛋白细胞内活性的差异可以决定空间细胞分选的方向，即使细胞表面亲和力没有差异，并提供新的分子工具来设计组织结构。
