Nuclear Origins of Cell-to-Cell Variability

During the past decade, it has become increasingly evident that there is variation in the transcriptome of genetically identical cells, even when grown in homogenous environments. This cell-to-cell variability has been shown to have a central role in processes ranging from stem cell differentiation to chemotherapy resistance. Given that many genes display extensive heterogeneity in their messenger RNA (mRNA) abundance on a per cell basis, understanding the nuclear sources of this variability is important for our fundamental grasp of nuclear function and stands to have clinical manifestations. In this chapter, we assess the contribution of different transcription regimes, nuclear architecture dynamics, RNA polymerase elongation, and gene copy number to transcriptome heterogeneity. We also discuss techniques that can be used to quantify single-cell mRNA abundance and conclude by commenting on future research directions.