Despite the central importance of stem cells in plant growth and development, the molecular signatures associated with them have not been revealed. Shoot apical meristems (SAMs) harbor a small set of stem cells located at the tip of each plant and they are surrounded by several million differentiating cells. This imposes a major limitation in isolating pure populations of stem cells for genomic analyses. We have developed a system to isolate pure populations of distinct cell types of the SAMs, including stem cells. We have used this system to profile gene expression from 4 different cell samples of SAMs. The cell sample-specific gene expression profiling has resulted in a highresolution gene expression map to reveal gene expression networks specific to individual spatial domains of SAMs. We demonstrate that the cell sample-specific expression profiling is sensitive in identifying rare transcripts expressed in a few specific subsets of cells of SAMs. Our extensive RNA in situ analysis reveals that the expression map can be used as a predictive tool in analyzing the spatial expression patterns of genes and it has led to the identification of unique gene expression patterns within the SAMs. Furthermore, our work reveals an enrichment of DNA repair and chromatin modification pathways in stem cells suggesting that maintenance of genome stability and flexible chromatin may be crucial for stem cell function. The gene expression map should guide future reverse genetics experiments, high-resolution analyses of cell-cell communication networks and epigenetic modifications.central zone ͉ CLAVATA3 ͉ fluorescence-activated cell sorting ͉ WUSCHEL S patiotemporal regulation of transcriptional programs mediated by cell-cell communication networks is crucial in stem cell maintenance (1, 2). Understanding the complexity of transcriptional programs requires a high resolution analysis of gene expression, preferably at a cell type-specific resolution (3). Shoot apical meristems (SAMs) of higher plants represent a dynamic and interconnected network of distinct cell types. In Arabidopsis thaliana, the SAM consists of Ϸ35 stem cells, located within the central zone (CZ) (4). Stem cells are surrounded by several million differentiating cells that are part of the adjacent peripheral zone (PZ) and developing organs. The cells of the Rib-meristem (RM) that are located just beneath the CZ provide positional cues necessary for stem cell maintenance ( Fig. 1 D and E). Earlier studies have revealed molecular mechanisms involved in stem cell maintenance (5). However, gene networks that underlie the stem cell maintenance process are far from understood. The development of high resolution gene expression map of distinct cell types of SAMs could enable network analysis of pathways involved in stem cell maintenance.Expression profiling studies of specific cell types have been performed on Arabidopsis root system (3, 6), however, studies on the SAMs have been restricted to experiments of the entire tissue (7). This is because the domains of specific...

BACKGROUND Chronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood. METHODS Using a nonhuman primate model of ethanol self-administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine and growth factor production in peripheral blood, lung and intestinal mucosa following twelve months of chronic ethanol exposure. RESULTS Ethanol exposure inhibited activation-induced production of growth factors HGF, G-CSF and VEGF by peripheral blood mononuclear cells (PBMC). Moreover, ethanol significantly reduced the frequency of colonic Th1 and Th17 cells in a dose-dependent manner. In contrast, we did not observe differences in lymphocyte frequency or soluble factor production in the lung of ethanol-consuming animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17 cytokine production, we compared expression levels of microRNAs in PBMC and intestinal mucosa. Our analysis revealed ethanol-dependent upregulation of distinct microRNAs in affected tissues (miR-181a and miR-221 in PBMC; miR-155 in colon). Moreover, we were able to detect reduced expression of the transcription factors STAT3 and ARNT, which regulate expression of VEGF, G-CSF and HGF and contain targets for these microRNAs. To confirm and extend these observations, PBMC were transfected with either mimics or antagomirs of miR181 and 221and protein levels of the transcription factors and growth factors were determined. Transfection of microRNA mimics led to a reduction in both STAT-3/ARNT as well as VEGF/HGF/G-CSF levels. The opposite outcome was observed when microRNA antagomirs were transfected CONCLUSION Chronic ethanol consumption significantly disrupts both peripheral and mucosal immune homeostasis, and this dysregulation may be mediated by changes in microRNA expression.

Summary The impacts of alcohol consumption on human health are complex and modulated by several factors such as patterns and amounts of drinking, genetics, the organ system studied, as well as the sex and the age of the user. There is strong evidence that chronic ethanol abuse is associated with increased morbidity and mortality, immunosuppression, and increased susceptibility to both bacterial and viral infections. In contrast, moderate alcohol consumption exerts positive effects including decreased mortality, and improved cardiovascular disease and insulin sensitivity. Interestingly, accumulating evidence also supports an immune boosting effect of moderate alcohol. In this editorial, we summarize the findings that support a positive effect of moderate alcohol on host immunity. We also discuss the limitations of the previous data and emphasize the importance of additional studies to uncover mechanisms for these immune-stimulating effects in order to extend these benefits to vulnerable segments of the population who cannot consume alcohol.

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