Institute of Biochemistry, ETH Zurich, 8093, Zürich, Switzerland.
Molecular Life Science PhD Program, Life Science Zurich Graduate School, 8057, Zürich, Switzerland.
Nat Commun. 2019 Apr 23;10(1):1901. doi: 10.1038/s41467-019-09413-5.
Asymmetric cell division is a major mechanism generating cell diversity. As cell cycle duration varies among cells in mammalian tissue culture cells, we asked whether their division asymmetry contributes to this variability. We identify among sibling cells an outlier using hierarchical clustering on cell cycle durations of granddaughter cells obtained by lineage tracking of single histone2B-labelled MDCKs. Remarkably, divisions involving outlier cells are not uniformly distributed in lineages, as shown by permutation tests, but appear to emerge from asymmetric divisions taking place at non-stochastic levels: a parent cell influences with 95% confidence and 0.5% error the unequal partitioning of the cell cycle duration in its two progenies. Upon ninein downregulation, this variability propagation is lost, and outlier frequency and variability in cell cycle durations in lineages is reduced. As external influences are not detectable, we propose that a cell-autonomous process, possibly involved in cell specialisation, determines cell cycle duration variability.
不对称细胞分裂是产生细胞多样性的主要机制。由于哺乳动物组织培养细胞中的细胞周期持续时间在不同细胞之间存在差异，我们想知道它们的分裂不对称性是否导致了这种可变性。我们通过对单个组蛋白 2B 标记的 MDCKs 进行谱系追踪获得的孙女细胞的细胞周期持续时间进行层次聚类，在兄弟姐妹细胞中识别出一个异常值。值得注意的是，如置换检验所示，涉及异常值细胞的分裂并非均匀分布在谱系中，而是似乎源自非随机水平的不对称分裂：父细胞以 95%的置信度和 0.5%的误差影响其两个后代细胞周期持续时间的不均匀分配。在 downregulating ninein 后，这种可变性传播就会丢失，谱系中异常值的频率和细胞周期持续时间的可变性也会降低。由于无法检测到外部影响，我们提出细胞自主过程，可能涉及细胞特化，决定了细胞周期持续时间的可变性。
