Quantitative Approaches to Heterogeneity and Growth Variability in Cell Populations

Clonal heterogeneity in cell populations with respect to properties such as growth rate, motility, metabolism or signaling, has been observed for some time. Unraveling the dynamics and the mechanisms giving rise to such variability has been the goal of recent work, largely aided by quantitative/ mathematical tools. Quantitative evaluation of cell-to-cell variability (heterogeneity) poses technical challenges that only recently are being overcome. Clearly, a mathematical theory of cellular heterogeneity could have fundamental implications. For instance, a theory of cell population growth variability, coupled with experimental measurements, may in the long term be crucial for an in-depth understanding of physiological processes such as stem cell expansion, embryonic development, tissue regeneration, or of pathological ones (e.g., cancer, fibrosis, tissue degeneration). We focus on recent advances, both theoretical and experimental, in quantification and modeling of the clonal variability of proliferation rates within cell populations. Our aim is to highlight a few stimulating examples from this fledgling and exciting field, in order to frame the issue and point to challenges and opportunities that lie ahead. Furthermore, we emphasize work carried out in cancer-related systems.