Cavendish Laboratory, Cambridge University, Cambridge CB2 1TN, United Kingdom.
Quantitative Life Sciences, The Abdus Salam International Centre for Theoretical Physics, 34151 Trieste, Italy.
Proc Natl Acad Sci U S A. 2021 May 4;118(18). doi: 10.1073/pnas.2016391118.
Despite a boost of recent progress in dynamic single-cell measurements and analyses in , we still lack a mechanistic understanding of the determinants of the decision to divide. Specifically, the debate is open regarding the processes linking growth and chromosome replication to division and on the molecular origin of the observed "adder correlations," whereby cells divide, adding roughly a constant volume independent of their initial volume. In order to gain insight into these questions, we interrogate dynamic size-growth behavior of single cells across nutrient upshifts with a high-precision microfluidic device. We find that the division rate changes quickly after nutrients change, much before growth rate goes to a steady state, and in a way that adder correlations are robustly conserved. Comparison of these data to simple mathematical models falsifies proposed mechanisms, where replication-segregation or septum completions are the limiting step for cell division. Instead, we show that the accumulation of a putative constitutively expressed "P-sector divisor" protein explains the behavior during the shift.
尽管最近在动态单细胞测量和分析方面取得了进展，但我们仍然缺乏对分裂决定因素的机制理解。具体来说，关于将生长和染色体复制与分裂联系起来的过程以及观察到的“adder 相关性”的分子起源的争论仍在继续，根据这种相关性，细胞分裂时，会大致增加一个与初始体积无关的恒定体积。为了深入了解这些问题，我们使用高精度微流控设备研究了单细胞在营养物质增加时的动态大小生长行为。我们发现，在生长率达到稳定状态之前，细胞分裂率在营养物质变化后很快发生变化，adder 相关性也得到了很好的保持。将这些数据与简单的数学模型进行比较，否定了复制-分离或隔膜完成是细胞分裂限制步骤的假设机制。相反，我们表明，一种假定的组成型表达的“P 区分裂器”蛋白的积累可以解释在转变过程中的行为。
