Engineering multilayered cellular structures The ability to program the manufacture of biological structures may yield new biomaterials or synthetic tissues and organs. Toda et al. engineered mammalian “sender” and “receiver” cells with synthetic cell surface ligands and receptors that controlled gene regulatory circuits based on Notch signaling. Programming the cells to express cell adhesion molecules and other regulatory molecules enabled spontaneous formation of multilayered structures, like those that form during embryonic development. The three-layered structures even showed regeneration after injury. Science, this issue p. 156 A synthetically engineered signaling system programs cell-cell contact–dependent pattern formation. A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multidomain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: Signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multicellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.

中文翻译：

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利用合成细胞间信号传导对自组织多细胞结构进行编程


工程多层细胞结构对生物结构制造进行编程的能力可能会产生新的生物材料或合成组织和器官。户田等人。用合成细胞表面配体和受体改造哺乳动物“发送者”和“接收者”细胞，这些配体和受体控制基于Notch信号传导的基因调控电路。对细胞进行编程以表达细胞粘附分子和其他调节分子，从而能够自发形成多层结构，就像胚胎发育过程中形成的结构一样。三层结构甚至在受伤后表现出再生能力。科学，本期第 14 页。 156 综合工程信号系统对细胞间接触依赖性模式的形成进行编程。多细胞组织自组织的一个共同主题是利用细胞间信号网络诱导形态变化。我们使用模块化的 synNotch juxtacrine 信号平台来设计人工遗传程序，其中特定的细胞-细胞接触诱导钙粘蛋白细胞粘附的变化。尽管它们很简单，但这些最小的细胞间程序足以产生具有自然发育系统特征的组装：强大的自组织成多域结构、精心设计的顺序组装、细胞类型分歧、对称性破坏以及损伤后的再生能力。这些网络驱动复杂结构形成的能力说明了将细胞信号传导与细胞分选互连的力量：信号诱导的空间重组改变了每个细胞接收的局部信号，导致细胞命运分支的迭代循环。 这些结果提供了对多细胞进化的见解，并展示了设计定制自组织组织或材料的潜力。