Mammalian tissues are composed of heterogeneous cells, interacting in highly structured microenvironments to achieve physiologic goals.To understand how cells operate in tissues we apply single molecule Fluorescense in-situ Hybridization (smFISH), a technique enabling visualization and quantification of individual mRNA molecules of any gene of interest in the intact tissue. I will describe applications of these approaches to meausre not only amounts of mRNA per cell but also transcription and mRNA degradation rates, as well as intra-cellular localization patterns. Using this approach we have uncovered bursty transcription of genes in the intact mouse liver and identified cellular strategies to dampen the associated single-cell variability in mRNA copy numbers.
