美国哈佛医学院Johan Paulsson和Richard Losick等研究人员合作发现，两种蛋白质之间的随机拮抗作用可以调控细菌细胞命运的转换。该项研究成果发表在2019年10月4日出版的《科学》上。

研究人员将调节突变体和体内重组与随机过程的理论相结合，表明枯草芽孢杆菌中细胞命运转换的特征，即离散状态、多代遗传和确定时机，这些可以通过两个组成型表达蛋白之间的简单随机竞争（形成失活的复合物）来解释。这种拮抗作用在细胞中很普遍，可以为更广泛地细胞命运确定提供了机制。

据悉，细胞命运决定的回路必须足够可变，从而使基因上相同的细胞能够形成多种命运，但还要确保这些状态是不同的、稳定地维持并与相邻细胞协调。长久以来的观点认为，这是通过涉及自我稳定反馈回路的调节网络来实现的，其将微小的差异转化为持久的细胞类型。

附：英文原文

Title: Stochastic antagonism between two proteins governs a bacterial cell fate switch

Author: Nathan D. Lord, Thomas M. Norman, Ruoshi Yuan, Somenath Bakshi, Richard Losick, Johan Paulsson

Issue&Volume: Volume 366 Issue 6461

Abstract: Cell fate decision circuits must be variable enough for genetically identical cells to adopt a multitude of fates, yet ensure that these states are distinct, stably maintained, and coordinated with neighboring cells. A long-standing view is that this is achieved by regulatory networks involving self-stabilizing feedback loops that convert small differences into long-lived cell types. We combined regulatory mutants and in vivo reconstitution with theory for stochastic processes to show that the marquee features of a cell fate switch in Bacillus subtilis—discrete states, multigenerational inheritance, and timing of commitments—can instead be explained by simple stochastic competition between two constitutively produced proteins that form an inactive complex. Such antagonistic interactions are commonplace in cells and could provide powerful mechanisms for cell fate determination more broadly.

DOI: 10.1126/science.aaw4506

Source:https://science.sciencemag.org/content/366/6461/116