A size-dependent division strategy accounts for leukemia cell size heterogeneity

Abstract

AbstractHeterogeneity in the size distribution of cancer cell populations is linked to drug resistance and invasiveness. However, understanding how such heterogeneity arises is still damped by the difficulties of monitoring the proliferation at the typical timescales of mammalian cells. Here, we show how to infer the growth regime and division strategy of leukemia cell populations using live cell fluorescence labeling and flow cytometry in combination with an analytical model where cell growth and division rates depend on powers of the size. We found that the dynamics of the size distribution of Jurkat T-cells is reproduced by (i) a sizer-like division strategy, with (ii) division times following an Erlang distribution and (iii) fluctuations up to ten percent of the inherited fraction of size at division. Overall, our apparatus can be extended to other cell types and environmental conditions allowing for a comprehensive characterization of the growth and division model different cells adopt.