Abstract
Growth pervades all areas of life from single cells to cell populations to tissues. However, cell size often fluctuates significantly from cell to cell and from generation to generation. Here we present a unified framework to predict the statistics of cell size variations within a lineage tree of a proliferating population. We analytically characterise (i) the distributions of cell size snapshots, (ii) the distribution within a population tree, and (iii) the distribution of lineages across the tree. Surprisingly, these size distributions differ significantly from observing single cells in isolation. In populations, cells seemingly grow to different sizes, typically exhibit less cell-to-cell variability and often display qualitatively different sensitivities to cell cycle noise and division errors. We demonstrate the key findings using recent single-cell data and elaborate on the implications for the ability of cells to maintain a narrow size distribution and the emergence of different power laws in these distributions.
Highlights
Cells decide when to divide based on their size
We find that the sensitivity to division errors Sp(CV2η) shown in Figure 2C increases with noise in cell size control in forward lineages for all size controls
We demonstrated that cells in populations exhibit different cell size, often exhibit lower cell-to-cell variability and display different sensitivities to division errors and cell cycle noise compared to cells in isolation
Summary
Cells decide when to divide based on their size. A key question is why cells grow to a certain size, how they maintain their sizes within a narrow distribution and what are the dominant sources of size variations. With the advent of single-cell traps such as the mother machine [2], the theoretical focus moved toward describing single cells over many divisions [13, 25,26,27] This path is more amenable to analysis because it considers only a single individual described by a discrete-time stochastic process or stochastic map [28]. We analyse (i) the size distributions of single dividing cells followed over time, (ii) the distribution in lineages across a population tree, (iii) the distribution across all cells in the tree, and (iv) the distributions of snapshots These measures stem from the same lineage tree and the same underlying stochastic process, we find that they can give quantitatively and qualitatively different results when size varies from cell to cell. Our findings highlight the significance of population dynamics for the analysis of cell size control and size homeostasis
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