The volumes and transcript counts of single cells reveal concentration homeostasis and capture biological noise.
Bottom Line: We compared three cell clones that differ only in the genomic integration site of an identical constitutively expressed reporter gene.We found that the cell-to-cell variability in the mRNA concentration is almost exclusively due to cell-to-cell variation in gene expression activity, whereas the cell-to-cell variation in mRNA number is larger, due to a significant contribution of cell volume variability.We concluded that the precise relationship between transcript number and cell volume sets the biological stochasticity of living cells.
Affiliation: Synthetic Systems Biology and Nuclear Organization Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.Show MeSH
Mentions: To assess biological mRNA noise, we require, in addition to mRNA number per cell, the volume of each cell. The same confocal z-stack images used for smFISH were used to determine the whole-cell, cytoplasmic, and nuclear volumes of the cells by tracing the contours of these compartments (Figure 2A). This allows us to obtain mRNA number, volume, and concentration data for each cell.
Affiliation: Synthetic Systems Biology and Nuclear Organization Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands.