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Lineage mapping has identified both proliferative and quiescent intestinal stem cells, but the molecular circuitry controlling stem cell quiescence is incompletely understood. By lineage mapping, we show Lrig1, a pan-ErbB inhibitor, marks predominately noncycling, long-lived stem cells that are located at the crypt base and that, upon injury, proliferate and divide to replenish damaged crypts. Transcriptome profiling of Lrig1(+) colonic stem cells differs markedly from the profiling of highly proliferative, Lgr5(+) colonic stem cells; genes upregulated in the Lrig1(+) population include those involved in cell cycle repression and response to oxidative damage. Loss of Apc in Lrig1(+) cells leads to intestinal adenomas, and genetic ablation of Lrig1 results in heightened ErbB1-3 expression and duodenal adenomas. These results shed light on the relationship between proliferative and quiescent intestinal stem cells and support a model in which intestinal stem cell quiescence is maintained by calibrated ErbB signaling with loss of a negative regulator predisposing to neoplasia.
Pubmed ID: 22464327 RIS Download
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A tool for performing multi-cluster gene functional enrichment analyses on large scale data (microarray experiments with many time-points, cell-types, tissue-types, etc.). It facilitates co-analysis of multiple gene lists and yields as output a rich functional map showing the shared and list-specific functional features. The output can be visualized in tabular, heatmap or network formats using built-in options as well as third-party software. It uses the hypergeometric test to obtain functional enrichment achieved via the gene list enrichment analysis option available in ToppGene.
View all literature mentionsSoftware platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.
View all literature mentionsToppGene Suite is a one-stop portal for gene list enrichment analysis and candidate gene prioritization based on functional annotations and protein interactions network. ToppGene Suite is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome. Functional annotation-based disease candidate gene prioritization uses a fuzzy-based similarity measure to compute the similarity between any two genes based on semantic annotations. The similarity scores from individual features are combined into an overall score using statistical meta-analysis.
View all literature mentionsA high-performance visualization tool for interactive exploration of large, integrated genomic datasets.
View all literature mentionsDatabase of microRNA target predictions and expression profiles. Target predictions are based on a development of the miRanda algorithm which incorporates current biological knowledge on target rules and on the use of an up-to-date compendium of mammalian microRNAs. MicroRNA expression profiles are derived from a comprehensive sequencing project of a large set of mammalian tissues and cell lines of normal and disease origin. This website enables users to explore: * The set of genes that are potentially regulated by a particular microRNA. * The implied cooperativity of multiple microRNAs on a particular mRNA. * MicroRNA expression profiles in various mammalian tissues. The web resource provides users with functional information about the growing number of microRNAs and their interaction with target genes in many species and facilitates novel discoveries in microRNA gene regulation. The microRNA Target Detection Software, miRanda, is an algorithm for finding genomic targets for microRNAs. This algorithm has been written in C and is available as an open-source method under the GPL.
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