Gene expression variability in clonal populations: Causes and consequences

Abstract

During the last decade it has been shown that among cell variation in gene expression plays an important role within clonal populations. Here, we provide an overview of the different mechanisms contributing to gene expression variability in clonal populations. These are ranging from inherent variations in the biochemical process of gene expression itself, such as intrinsic noise, extrinsic noise and bistability to individual responses to variations in the local micro-environment, a phenomenon called phenotypic plasticity. Also genotypic variations caused by clonal evolution and phase variation can contribute to gene expression variability. Consequently, gene expression studies need to take these fluctuations in expression into account. However, frequently used techniques for expression quantification, such as microarrays, RNA sequencing, quantitative PCR and gene reporter fusions classically determine the population average of gene expression. Here, we discuss how these techniques can be adapted towards single cell analysis by integration with single cell isolation, RNA amplification and microscopy. Alternatively more qualitative selection-based techniques, such as mutant screenings, in vivo expression technology (IVET) and recombination-based IVET (RIVET) can be applied for detection of genes expressed only within a subpopulation. Finally, differential fluorescence induction (DFI), a protocol specially designed for single cell expression is discussed.

• Bistability
• phenotypic plasticity
• single-cell
• stochasticity

Acknowledgements

We are grateful for the funding received by the Institute for the Promotion of Innovation through Science and Technology in Flanders under grant IWT-SBO 120050 (NEMOA) and through PhD fellowship to SR, the European Commission's Seventh Framework Programme (FP7/2007(2013) under the grant agreement COATIM (Project no. 278425), the KU Leuven (IDO/11/008, PF/NATAR) and the F.W.O. (Fund for Scientific Research – Flanders (Belgium)) through a postdoctoral fellowship to HS.

Declaration of interest

The authors report no declarations of interest.