DOI：10.1038/nature14318 作者：Oded Sandler
摘要 : 细胞周期长短的变化被认为是由基本分子过程(如信使RNA或蛋白的生成和降解)的随机波动造成的。基于一个能够概括他们数据的完全确定的模型，本文作者提出，所观察到的响应于抗生素或药物处理而出现的细胞异质性也许可以归因于不像以前所认为的那么随机的过程。
基于对数以千计哺乳动物细胞的细胞周期长短所做的精确测定，现在Nathalie Balaban及同事报告了 “表细胞”(cousin cell)之间的反直觉关联，而这种关联在 “母细胞”(mother cell)和 “子细胞”(daughter cell)之间却没有。
Stochastic processes in cells are associated with fluctuations in mRNA1, protein production and degradation2, 3, noisy partition of cellular components at division4, and other cell processes. Variability within a clonal population of cells originates from such stochastic processes, which may be amplified or reduced by deterministic factors5. Cell-to-cell variability, such as that seen in the heterogeneous response of bacteria to antibiotics, or of cancer cells to treatment, is understood as the inevitable consequence of stochasticity. Variability in cell-cycle duration was observed long ago; however, its sources are still unknown. A central question is whether the variance of the observed distribution originates from stochastic processes, or whether it arises mostly from a deterministic process that only appears to be random. A surprising feature of cell-cycle-duration inheritance is that it seems to be lost within one generation but to be still present in the next generation, generating poor correlation between mother and daughter cells but high correlation between cousin cells6. This observation suggests the existence of underlying deterministic factors that determine the main part of cell-to-cell variability. We developed an experimental system that precisely measures the cell-cycle duration of thousands of mammalian cells along several generations and a mathematical framework that allows discrimination between stochastic and deterministic processes in lineages of cells. We show that the inter- and intra-generation correlations reveal complex inheritance of the cell-cycle duration. Finally, we build a deterministic nonlinear toy model for cell-cycle inheritance that reproduces the main features of our data. Our approach constitutes a general method to identify deterministic variability in lineages of cells or organisms, which may help to predict and, eventually, reduce cell-to-cell heterogeneity in various systems, such as cancer cells under treatment.
来源： Nature 浏览次数：4