#Median xl level challenges series#

Received: Accepted: ApPublished: June 13, 2019Д¬opyright: В© 2019 Momiji et al. MacGregor, University of Edinburgh, UNITED KINGDOM (2019) Disentangling juxtacrine from paracrine signalling in dynamic tissue. The method and model developed here are generic and can be used in the study of other signalling systems that show space-time coordinated behaviour.Д¬itation: Momiji H, Hassall KL, Featherstone K, McNamara AV, Patist AL, Spiller DG, et al.

The study develops a mathematical model that can reproduce realistic levels of space-time coordinated gene expression.

This discovery raised a new question, namely, what kind of cellular communication mediates such a space-time organization? In this study, by developing a statistical method that involves network theory, we show that such unexpected behaviour involves contact-driven inter-cell signalling.

However, recent experiments using real-time imaging techniques at a single-cell resolution have revealed prolactin gene transcription to be highly dynamic and stochastic in nature, while displaying clear tissue-scale space-time coordination. Production of such an important protein needs to be regulated tightly, and therefore one might imagine that its gene expression is largely static. In mammals it is crucial for milk production and reproductive function. Prolactin is a major hormone product of the pituitary gland, the central endocrine regulator found underneath the brain. The developed model is expected to serve as the prototype for the further study of tissue-level organised gene expression for epigenetically regulated genes, such as prolactin. We developed a computational model that involves an inter-cell juxtacrine coupling, yielding simulation results that show space-time coordination in the transcription level that is in agreement with the above analysis. To further determine whether the coupling is coordinating transcription or post-transcriptional activities we used stochastic switch modelling to infer the transcriptional profiles of cells and estimated their similarity measures to deduce that their spatial cellular coordination involves coupling of transcription via juxtacrine signalling. The analysis presented here suggests that juxtacrine signalling dominates.

#Median xl level challenges series#

The degree of similarity between two expression time series was studied in terms of two distance measures, Euclidean and geodesic, the latter being a network-theoretic distance defined to be the minimal number of edges between nodes, and this was used to discriminate between juxtacrine from paracrine signalling. To determine the type of interaction between cells we developed a statistical model. However, it still remains an open question as to what kind of cellular communication mediates the observed space-time organization. Having significantly improved the resolution of real-time-single-cell-GFP-imaging, the authors recently revealed that prolactin gene transcription is highly dynamic and stochastic yet shows space-time coordination in an intact tissue slice. Despite its physiological importance, the cell-level mechanisms of prolactin production are not well understood. Prolactin is a major hormone product of the pituitary gland, the central endocrine regulator.