Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels

Abstract

The transcriptional machinery in individual cells is controlled by a relatively small number of molecules, which may result in stochastic behavior in gene activity. Because of technical limitations in current collection and recording methods, most gene expression measurements are carried out on populations of cells and therefore reflect average mRNA levels. The variability of the transcript levels between different cells remains undefined, although it may have profound effects on cellular activities. Here we have measured gene expression levels of the five genes ActB, Ins1, Ins2, Abcc8, and Kcnj11 in individual cells from mouse pancreatic islets. Whereas Ins1 and Ins2 expression show a strong cell-cell correlation, this is not the case for the other genes. We further found that the transcript levels of the different genes are lognormally distributed. Hence, the geometric mean of expression levels provides a better estimate of gene activity of the typical cell than does the arithmetic mean measured on a cell population.

Figure 1.

Histograms showing the expression levels of 96 cells expressing ActB in logarithmic and linear scale (inset). Logarithms of transcript levels are mean-centered for the two glucose concentrations. Solid line describes lognormal distribution centered on the geometric mean (2.06) of the ActB expression levels. Inset shows histogram of the expression levels in linear scale.

Figure 2.

(A) Histograms of Ins1 expression levels in cells incubated in 5 mM (bottom) and 20 mM (top) glucose. Horizontal axis has logarithmic scale, which is identical in the two histograms. Scale on the vertical axis indicates the cell count in each histogram bin. (B) Corresponding histograms for Ins2 expression levels.