51. Drosophila intestinal stem and progenitor cells are major sources and regulators of homeostatic niche signals
- Author
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Doupé, David P, Marshall, Owen J, Dayton, Hannah, Brand, Andrea H, Perrimon, Norbert, Brand, Andrea [0000-0002-2089-6954], and Apollo - University of Cambridge Repository
- Subjects
insulin ,Biological Sciences ,microenvironment ,Intestines ,niche ,stem cells ,Animals ,Drosophila Proteins ,Homeostasis ,Drosophila ,Stem Cell Niche ,epithelial homeostasis ,Signal Transduction ,Developmental Biology - Abstract
Significance Most epithelia are turned over throughout adult life as cells are lost from the surface and replaced by the proliferation of stem cells. Precise regulation of stem cells by signals from the local microenvironment or niche is important to maintain epithelial homeostasis. Here, using intestinal stem cells of the Drosophila midgut as a model system, we use transcriptome profiling to identify genes expressed specifically in stem and progenitor cells and not their differentiated daughters. We find that stem and progenitor cells express ligands of major developmental signaling pathways to both contribute to the niche and regulate the production of niche signals from other cell types., Epithelial homeostasis requires the precise balance of epithelial stem/progenitor proliferation and differentiation. While many signaling pathways that regulate epithelial stem cells have been identified, it is probable that other regulators remain unidentified. 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 eiger 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 microenvironmental niche through the expression of autocrine and paracrine factors.
- Published
- 2018