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.

HPV16‐E6 mRNA is superior to cytokeratin 19 mRNA as a molecular marker for the detection of disseminated tumour cells in sentinel lymph nodes of patients with cervical cancer by quantitative reverse‐transcription PCR

“…The performed log transformation is consistent with the observed log-normal distribution of mRNA levels. 34 Regardless of the same histological classification we observed a broad distribution of transcript copy numbers. This may be due to a nonuniform intranodal distribution of tumour cells, different levels of gene expression in the tumours per se or highly variable numbers of tumour cells in pathologically conspicuous lymph nodes.…”

A causal role for hyperinsulinemia in obesity

“…Ins2 can be detected earlier in murine development and has a broader tissue distribution (Deltour et al 1993, Fan et al 2009, Mehran et al 2012. Murine Ins1 expression and promoter activity are largely restricted to the pancreas (Mehran et al 2012, Thorens et al 2015, and it does not contribute as much to pancreatic insulin production as Ins2, except in the mouse embryo during the early stages of pancreatic development (Wentworth et al 1986, Linde et al 1989, Deltour et al 1993, Bengtsson et al 2005. Complete inactivation of both Ins genes in mice (i.e.…”

Comment on: Marchand and Polychronakos (2007) Evaluation of Polymorphic Splicing in the Mechanism of the Association of the Insulin Gene with Diabetes: Diabetes 56:709–713

“…This is relevant to the early development of immunological tolerance, but it does not closely model the "stressed " ␤-cells of a pre-diabetic individual. It has been shown in normal mouse islets that some cells conduct more insulin gene transcription compared with others in response to glucose (4). In the observed model, the use of arithmetic means for the cell population obscures this reality.…”