Distribution of miRNA expression across human tissues

Abstract

We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10−8) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).

An integrated expression atlas of miRNAs and their promoters in human and mouse

“…A cell type specificity index, analogous to the previously defined tissue specificity index 29 , was calculated to quantify the cell type specificity of miRNA expression across the FANTOM5 collection of primary cell types (Table S13). Previously described highly cell-type-specific miRNAs included miR-122-5p, miR-142-5p, and miR-302a-5p, which were enriched in hepatocytes, leukocytes, and pluripotent stem cells, respectively (Figure 2d).…”

“…Compared to existing miRNA expression atlases 29,38 , the FANTOM5 atlas covers the widest range of normal primary cells, enabling detailed analyses of miRNA expression and their contribution to establishing and maintaining cell type identity. The candidate miRNAs not reported previously were in particular highly specific to cell type, and may therefore be missed in miRNA profiling studies in tissues rather than in specific cell types.…”

“…Following the definition of the tissue specificity index (TSI) 29 , we defined the cell type specificity index of miRNA j as…”

Distribution of microRNA biomarker candidates in solid tissues and body fluids

“…5 Using microarrays we recently published a Human miRNA Tissue Atlas, which is freely accessible (www.ccb.uni-saarland.de/tissueatlas). 6 In this study we first investigated the influence of degradation on tissue miRNA patterns and then profiled altogether 31 different organs from 2 corpses. Tissue patterns were generated for miRNAs from the most recent versions 20 and 21 of the miRBase.…”

miRNA assays in the clinical laboratory: workflow, detection technologies and automation aspects

“…The remarkable stability of miRNAs in blood, serum or plasma makes respective tests particularly interesting for the clinical routine as sample storage, handling and shipment may not be as critical for miRNAs as for other biomarkers [23][24][25], as long as reasonable boundary conditions are taken into account [26]. It is barely understood where the blood-borne miRNA is originating from, but it is plausible that it is derived from multiple sources -certainly from body tissues that show specific miRNA patterns [27], but also from white blood cells, platelets [28,29], and even microvesicles [30,31], respectively. A miRNA species that is highly de-regulated in a particular diseased tissue may therefore exhibit only a subtle change in concentration level in blood, as the latter sample type obtains the same miRNA from multiple sources.…”