Expression Profiling of Human Immune Cell Subsets Identifies miRNA-mRNA Regulatory Relationships Correlated with Cell Type Specific Expression

Abstract

Blood consists of different cell populations with distinct functions and correspondingly, distinct gene expression profiles. In this study, global miRNA expression profiling was performed across a panel of nine human immune cell subsets (neutrophils, eosinophils, monocytes, B cells, NK cells, CD4 T cells, CD8 T cells, mDCs and pDCs) to identify cell-type specific miRNAs. mRNA expression profiling was performed on the same samples to determine if miRNAs specific to certain cell types down-regulated expression levels of their target genes. Six cell-type specific miRNAs (miR-143; neutrophil specific, miR-125; T cells and neutrophil specific, miR-500; monocyte and pDC specific, miR-150; lymphoid cell specific, miR-652 and miR-223; both myeloid cell specific) were negatively correlated with expression of their predicted target genes. These results were further validated using an independent cohort where similar immune cell subsets were isolated and profiled for both miRNA and mRNA expression. miRNAs which negatively correlated with target gene expression in both cohorts were identified as candidates for miRNA/mRNA regulatory pairs and were used to construct a cell-type specific regulatory network. miRNA/mRNA pairs formed two distinct clusters in the network corresponding to myeloid (nine miRNAs) and lymphoid lineages (two miRNAs). Several myeloid specific miRNAs targeted common genes including ABL2, EIF4A2, EPC1 and INO80D; these common targets were enriched for genes involved in the regulation of gene expression (p<9.0E-7). Those miRNA might therefore have significant further effect on gene expression by repressing the expression of genes involved in transcriptional regulation. The miRNA and mRNA expression profiles reported in this study form a comprehensive transcriptome database of various human blood cells and serve as a valuable resource for elucidating the role of miRNA mediated regulation in the establishment of immune cell identity.

Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects

“…Here we demonstrate that, at baseline, O 3 responders have lower expression of three miRNAs, namely miR-143, miR-145, and miR-199a*. Interestingly, miR-143 is known to play a role in neutrophil influx (6) and hence may contribute to the constitutively primed airway of responders. These data suggest that interindividual differences in inflammatory responsiveness to O 3 may be regulated at the miRNA level.…”

“…Thus in this study it was important to identify cell-specific miRNAs that could act as potential confounders since some miRNAs are preferentially expressed in certain cell types (6) and O 3 exposure caused a significant increase in neutrophils in most of our subjects. A comparison of the 10 O 3 -responsive miRNAs to a database of immune cell-specific miRNAs (6) showed that miR-143 and miR-223 are immune cell specific and overabundant in neutrophils and myeloid cells. Interestingly, miR-143 expression changes were significantly correlated with % change in PMN counts, suggesting that miR-143 may serve as a biomarker for increases in PMN cell populations.…”

“…To assess whether the O3-induced changes in miRNA expression profiles were attributable to changes in the distribution of cell populations and hence a confounding factor, the O3-responsive miRNAs were compared with miRNAs that have been identified as specifically being expressed in certain immune cell populations. Findings from a recent investigation (6) were used in the comparison, where authors performed genomewide miRNA expression profiling for nine human immune cell subsets: neutrophils, eosinophils, monocytes, B cells, natural killer cells, CD4 T cells, CD8 T cells, myeloid dendritic cells, and plasmacytoid dendritic cells (6). Cell type-specific miRNAs were identified as those specifically expressed on one of the evaluated immune cell types (6).…”

“…Findings from a recent investigation (6) were used in the comparison, where authors performed genomewide miRNA expression profiling for nine human immune cell subsets: neutrophils, eosinophils, monocytes, B cells, natural killer cells, CD4 T cells, CD8 T cells, myeloid dendritic cells, and plasmacytoid dendritic cells (6). Cell type-specific miRNAs were identified as those specifically expressed on one of the evaluated immune cell types (6). This list of immune cell type-specific miRNAs was compared against the miRNAs identified as O3 responsive in this study.…”

Role of microRNA-150 in solid tumors

“…Monticelli et al were the first to investigate the systematic miRNA gene profiling in hematopoietic cells, demonstrating that its profiling was different from non-hematopoietic cells (15). As an important hematopoietic cell-specific miRNA, miR-150 is mainly expressed in B-cells, T-cells and natural killer cells, and plays a critical role in the differentiation of numerous hematopoietic cell lineages, particularly in lymphocyte development and function (14,16). In addition, a recent study has identified that serum circulating miR-150 is a sensor of general lymphocyte activation and may serve as a biomarker of human lymphocyte activation in healthy and disease conditions (17).…”