CAS Key Laboratory for Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Chem Biol. 2023 Sep;19(9):1097-1104. doi: 10.1038/s41589-023-01302-9. Epub 2023 Mar 23.
The global regulation of cell growth rate on gene expression perturbs the performance of gene networks, which would impose complex variations on the cell-fate decision landscape. Here we use a simple synthetic circuit of mutual repression that allows a bistable landscape to examine how such global regulation would affect the stability of phenotypic landscape and the accompanying dynamics of cell-fate determination. We show that the landscape experiences a growth-rate-induced bifurcation between monostability and bistability. Theoretical and experimental analyses reveal that this bifurcating deformation of landscape arises from the unbalanced response of gene expression to growth variations. The path of growth transition across the bifurcation would reshape cell-fate decisions. These results demonstrate the importance of growth regulation on cell-fate determination processes, regardless of specific molecular signaling or regulation.
细胞生长速率的全局调控会扰乱基因网络的性能，这将对细胞命运决定景观施加复杂的变化。在这里，我们使用相互抑制的简单合成电路，允许双稳态景观来检查这种全局调控如何影响表型景观的稳定性和伴随的细胞命运决定的动力学。我们表明，景观经历了由单稳定性和双稳定性之间的生长速率诱导分岔。理论和实验分析表明，这种景观的分岔变形源于基因表达对生长变化的不平衡响应。跨越分岔的生长过渡路径将重塑细胞命运的决定。这些结果表明，无论特定的分子信号或调控如何，生长调控对细胞命运决定过程都很重要。
