RT Journal Article
SR Electronic
T1 Mathematical models incorporating a multi-stage cell cycle explain synchronisation in proliferation experiments
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 557702
DO 10.1101/557702
A1 Sean T. Vittadello
A1 Scott W. McCue
A1 Gency Gunasingh
A1 Nikolas K. Haass
A1 Matthew J. Simpson
YR 2019
UL http://biorxiv.org/content/early/2019/02/22/557702.abstract
AB We present a suite of experimental data showing that cell proliferation assays, prepared using standard protocols thought to lead to asynchronous populations, persistently exhibit synchronisation. Our experiments use novel fluorescent cell cycle tracking to illustrate synchronisation by highlighting oscillatory subpopulations within the total population of cells. In a more standard setting, without cell cycle tracking, we can only quantify the total cell population and we show that the total cell population data in all our experiments appears to grow exponentially. These observations appear to be conflicting. One potential explanation of these observations is the impact of cell synchronisation, and we show how to reconcile these conflicting observations using a multi-stage model of cell proliferation. Overall, our study has important implications for understanding and improving experimental reproducibility. In summary, while the total population of cells appears to grow exponentially, consistent with an asynchronous population of cells, careful experimental interrogation confirms that standard protocols lead to persistent synchronisation. This normally hidden feature could explain irreproducibility of experiments that examine the role of antimitotic drugs.