Project description:Epithelial homeostasis requires the precise balance of epithelial stem/progenitor proliferation and differentiation. While many of the signaling pathways that regulate epithelial stem cells have been identified, less is known about their targets or crosstalk between them. Here, we use gene expression profiling by targeted DamID to identify the stem/progenitor specific transcription and signaling factors in the Drosophila midgut. Many signaling pathway components, including ligands of most major pathways, exhibit stem/progenitor specific expression and have regulatory regions bound by both intrinsic and extrinsic transcription factors. In addition to previously identified stem/progenitor-derived ligands, we show that both the insulin-like factor Ilp6 and TNF ligand egr are specifically expressed in the stem/progenitors and regulate normal tissue homeostasis. We propose that intestinal stem cells not only integrate multiple signals but also contribute to and regulate the homeostatic signaling micro-environmental niche through the expression of autocrine and paracrine factors.
Project description:Imbalance in intestinal stem cell (ISC) homeostasis leads to cancer and metabolic disease. Therefore intense efforts are underway to understand ISC hierarchy and the niche signals that control stem cell fate. Several ISC populations have been described according to their marker expression, cell-cycle behavior and lineage potential. Actively cycling Lgr5+ ISCs ensure homeostatic renewal. A less well-defined and minor population of quiescent and label-retaining cells (LRCs) is viewed as a reserve stem cell pool. However, the existence of quiescent stem cells distinct from the Lgr5+ ISCs is controversial. Indeed, recent findings identified quiescent intestinal cells as a subpopulation of Lgr5+ ISCs that are committed to the secretory fate, but the signals that maintain and activate quiescent cells/LRCs remain elusive.
Project description:We demonstrate the conserved Hh-GLI2-mediated chromatin and transcriptional regulation of both stomach and intestinal stromal stem cell niche signals. Analyses of H3K27ac marks demonstrate GLI2-mediated transcription regulation of stem cell niche signals such as Wnt ligand genes, through enhancers conserved between the stomach and intestine.
Project description:We demonstrate the conserved Hh-GLI2-mediated chromatin and transcriptional regulation of both stomach and intestinal stromal stem cell niche signals. Analyses of H3K27ac marks demonstrate GLI2-mediated transcription regulation of stem cell niche signals such as Wnt ligand genes, through enhancers conserved between the stomach and intestine.
