From measuring noise toward integrated single-cell biology

Abstract

A single cell is inherently noisy. This noise is observed as a variability or heterogeneity between individual cells' responses in an isogenic population, and emerges from fundamental physical process governing state of the cell over time. In practice, states of two seemingly identical cells may be different in the same environment; and in fact the behavior of the population average my not correspond to any of the individual cells. Recent decades brought a technological breakthrough in many areas in our ability to measure and interpret cellular heterogeneity, including live-cell imaging (Spiller et al., 2010) and genome-wide epigenetic and expression analyses (in particular next generation sequencing) (Chattopadhyay et al., 2014). The emerging picture is that the cellular noise is not a nuisance, but a ubiquitous functional trait that could perhaps be therapeutically exploited. Here we discuss relevant technological advances as well as postulate the need for more quantitative and integrated temporal single cell biology approaches to study cellular heterogeneity.