Inferring steady state single-cell gene expression distributions from analysis of mesoscopic samples

Here we present a simple model for transcript levels based on Poisson statistics and provide supporting experimental evidence for genes known to be expressed at high, moderate, and low levels.Although the model describes a microscopic process occurring at the level of an individual cell, the supporting data we provide uses a small number of cells where the echoes of the underlying stochastic processes can be seen. Not only do these data confirm our model, but this general strategy opens up a potential new approach, Mesoscopic Biology, that can be used to assess the natural variability of processes occurring at the cellular level in biological systems.In the study of biological processes, most of our observations are based on measurements made on a macroscopic scale, such as a piece of tissue or the collection of cells in a tissue culture dish, while the processes themselves are driven by events that occur at a microscopic scale representing events within each individual cell. The paradox here is that, macroscopically, biological processes often seem deterministic and are driven by what we observe as the average behaviour of millions of cells, but microscopically we expect the biology, driven by molecules that have to come together and interact in a complex environment, to have a stochastic component. Indeed, studies of transcriptional regulation at the single cell level have uncovered examples of non-uniform behaviour of gene expression in genetically identical cells. Levsky et al. [1] were among the first to profile gene expression levels in single cells and their results provided direct evidence of variable expression patterns in otherwise identical cells. Ozbudak et al. [2] quantified the direct effect that fluctuations in molecular species had on the variation of gene expression levels in isogenic cells. By independently modifying transcription and translation rates of a single fluorescent reporter protein, they were able to observe the downstream effects this h