Abstract

Every cell biologist who has used a microscope knows that single cells in a population display variable behavior (1). Although heterogeneity between single cells is obvious in tissues and organisms, it can also be observed in populations of monoclonal cells that have been cultured under identical conditions. Besides having stochastic sources (2, 3), phenotypic cell-to-cell variability among genetically identical cells can be deterministic and regulated, in both prokaryotic and mammalian cells (4, 5). Molecular and cell biologists have traditionally ignored this phenomenon, in part because of technical limitations, but also because, historically, research has focused on mechanisms and processes that are common between cells. However, the mechanisms that make them different are likely to be equally important. Embracing this cell-to-cell variability as a fact in our scientific understanding requires a paradigm shift, but it will be necessary. In fact, it may be a strong boost for the field by uncovering novel and previously overlooked mechanisms of regulation at the cell population level.