Cell Population Growth Kinetics in the Presence of Stochastic Heterogeneity of Cell Phenotype

Abstract

Recent studies at individual cell resolution have revealed phenotypic heterogeneity in nominally clonal tumor cell populations. The heterogeneity affects cell growth behaviors, which can result in departure from the idealized exponential growth. Here we measured the stochastic time courses of growth of an ensemble of populations of HL60 leukemia cells in cultures, starting with distinct initial cell numbers to capture the departure from the exponential growth model in the initial growth phase. Despite being derived from the same cell clone, we observed significant variations in the early growth patterns of individual cultures with statistically significant differences in growth kinetics and the presence of subpopulations with different growth rates that endured for many generations. Based on the hypothesis of existence of multiple inter-converting subpopulations, we developed a branching process model that captures the experimental observations.

Determine transposable genes when the orders of genes are different

“…Other mathematical tools, such as dynamical system [65, 62] and partial differential equations [49], can also be applied. Models in this paper can also be used to explain some phenomena in other cancer types, not necessarily for myeloproliferative neoplasm [60]. Besides, our results might provide insights for cancer treatment [45], which might needs complicated policy optimization [58, 59].…”

Cell-state transitions and frequency-dependent interactions among subpopulations together explain the dynamics of spontaneous epithelial-mesenchymal heterogeneity in breast cancer

“…Unfortunately, however, the above studies did not explicitly report the growth rates of E-M cell populations in each scenario, thus missing out inadvertently on contributions of different growth rates on E-M heterogeneity dynamics. Measuring any change(s) in growth rates is crucial for two reasons: 1) growth rate differences among subpopulations impact the population-level composition 15,16 , and 2) EMT is also known to slows down cell proliferation 17,18 , and thus, inhibition of EMT may not only reduce cell-state transition but may increase the proliferation rate 19 . Therefore, the relative contribution of various interconnected cell-autonomous and non-cell autonomous effects on population dynamics of EMT and MET remains poorly understood.…”