Department of Biosciences, Rice University, Houston, TX, USA.
PhD Program in Systems, Synthetic, and Physical Biology, Rice University, Houston, TX, USA.
Nat Chem Biol. 2019 Sep;15(9):917-924. doi: 10.1038/s41589-019-0339-x. Epub 2019 Aug 12.
We describe a synthetic genetic circuit for controlling asymmetric cell division in Escherichia coli in which a progenitor cell creates a differentiated daughter cell while retaining its original phenotype. Specifically, we engineered an inducible system that can bind and segregate plasmid DNA to a single position in the cell. Upon cell division, colocalized plasmids are kept by one and only one of the daughter cells. The other daughter cell receives no plasmid DNA and is irreversibly differentiated from its sibling. In this way, we achieved asymmetric cell division through asymmetric plasmid partitioning. We then used this system to achieve physical separation of genetically distinct cells by tying motility to differentiation. Finally, we characterized an orthogonal inducible circuit that enables the simultaneous asymmetric partitioning of two plasmid species, resulting in cells that have four distinct differentiated states. These results point the way toward the engineering of multicellular systems from prokaryotic hosts.
我们描述了一个用于控制大肠杆菌不对称细胞分裂的合成遗传回路,其中祖细胞在保留其原始表型的同时产生一个分化的子细胞。具体来说,我们设计了一个可诱导的系统,该系统可以将质粒 DNA 结合并分配到细胞中的一个单一位置。在细胞分裂时,聚集在一起的质粒被一个而且只有一个子细胞保留。另一个子细胞不接收任何质粒 DNA,并与其同胞不可逆地分化。通过这种方式,我们通过不对称质粒分配实现了不对称细胞分裂。然后,我们通过将运动与分化联系起来,使用该系统实现了遗传上不同的细胞的物理分离。最后,我们描述了一个正交的可诱导回路,该回路可以实现两种质粒物种的同时不对称分配,从而产生具有四种不同分化状态的细胞。这些结果为从原核宿主工程构建多细胞系统指明了方向。