Asymmetric division events promote variability in cell cycle duration in animal cells and E. coli
Variations in cell cycle duration between cells occur naturally but the mechanisms are largely unknown. A recent publication by the Kroschewski group in Nature Communications shows that large differences in granddaughter cell cycle duration are also driven by asymmetric divisions.
Asymmetric cell division is a major mechanism generating cell diversity. As cell cycle duration varies amongst cells in diverse cell systems, we asked whether their division asymmetry contributes to this variability. We identify amongst sibling cells an outlier using hierarchical clustering on cell cycle durations of granddaughter cells (3:1 motif) obtained by lineage tracking of single MDCKs. Remarkably, divisions involving outlier cells are not uniformly distributed in lineages, as shown by permutation tests, but appeared to emerge from asymmetric divisions taking place at non-stochastic levels: a parent cell influences the unequal partitioning of the cell cycle duration in its two progenies. Upon ninein downregulation, this variability propagation was lost and outlier frequency and variability in cell cycle durations in lineages were reduced. As external influences were not detectable in the MDCK cells and the outliers propagate non-stochastically in diverse cell systems (mouse haematopoietic stem cells, in differentiation medium, C. elegans, and E. coli, when cultured at pH6.0) at non-stochastic levels, we propose that a cell-autonomous process, possibly involved in cell-specialization, determines cell cycle duration variability.
Link to the publication in external page "Nature Communications".