Cell size control and gene expression homeostasis in single-cells

Abstract

Growth of a cell and its subsequent division into daughters is a fundamental aspect of all cellular living systems. During these processes, how do individual cells correct size aberrations so that they do not grow abnormally large or small? How do cells ensure that the concentration of essential gene products are maintained at desired levels, in spite of dynamic/stochastic changes in cell size during growth and division? Both these questions have fascinated researchers for over a century. We review how advances in singe-cell technologies and measurements are providing unique insights into these questions across organisms from prokaryotes to human cells. More specifically, diverse strategies based on timing of cell-cycle events, regulating growth, and number of daughters are employed to maintain cell size homeostasis. Interestingly, size homeostasis often results in size optimality – proliferation of individual cells in a population is maximized at an optimal cell size. We further discuss how size-dependent expression or gene-replication timing can buffer concentration of a gene product from cell-to-cell size variations within a population. Finally, we speculate on an intriguing hypothesis that specific size control strategies may have evolved as a consequence of gene-product concentration homeostasis.