美国加州理工大学Michael B. Elowitz及其研究团队研制了可在哺乳动物细胞中稳定存在的合成电路。该研究于2022年1月21日发表于国际学术期刊《科学》杂志。

研究人员研发了MultiFate，这是一种自然发生的合成电路，有利于哺乳动物细胞中长期、可控和可扩展多稳定性维持。MultiFate使用工程化的锌指转录因子，这些转录因子以同源二聚体的形式开启转录自我激活，并通过异源二聚体形式相互抑制。使用基于模型的设计，研究人员设计了MultiFate电路，可生成多达7个状态且每个状态至少可稳定18天。

MultiFate可通过外部输入控制状态切换和调节状态稳定性，并且可以通过额外的转录因子进行扩展。这些结果为在哺乳动物细胞中设计多细胞行为提供了基础。

据介绍，在多细胞生物中，基因调控回路通过多稳定性特征产生数千种分子不同的、有丝分裂可遗传状态。设计合成多稳态电路将有利于深入理解自然细胞命运控制电路的结构，以及研发设计需要不同细胞类型之间相互作用的多细胞程序。

附：英文原文

Title: Synthetic multistability in mammalian cells

Author: Ronghui Zhu, Jesus M. del Rio-Salgado, Jordi Garcia-Ojalvo, Michael B. Elowitz

Issue&Volume: 2022-01-21

Abstract: In multicellular organisms, gene regulatory circuits generate thousands of molecularly distinct, mitotically heritable states through the property of multistability. Designing synthetic multistable circuits would provide insight into natural cell fate control circuit architectures and would allow engineering of multicellular programs that require interactions among distinct cell types. We created MultiFate, a naturally inspired, synthetic circuit that supports long-term, controllable, and expandable multistability in mammalian cells. MultiFate uses engineered zinc finger transcription factors that transcriptionally self-activate as homodimers and mutually inhibit one another through heterodimerization. Using a model-based design, we engineered MultiFate circuits that generate as many as seven states, each stable for at least 18 days. MultiFate permits controlled state switching and modulation of state stability through external inputs and can be expanded with additional transcription factors. These results provide a foundation for engineering multicellular behaviors in mammalian cells.

DOI: abg9765

Source: https://www.science.org/doi/10.1126/science.abg9765