Asymmetric division events promote variability in cell cycle duration in animal cells and Escherichia coli.

Abstract

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.