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Drosophila intestinal stem and progenitor cells are major sources and regulators of homeostatic niche signals.

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Doupé, David P 
Marshall, Owen J 
Dayton, Hannah 
Brand, Andrea H 
Perrimon, Norbert 


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.



epithelial homeostasis, insulin, microenvironment, niche, stem cells, Animals, Drosophila, Drosophila Proteins, Homeostasis, Intestines, Signal Transduction, Stem Cell Niche, Stem Cells

Journal Title

Proc Natl Acad Sci U S A

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Proceedings of the National Academy of Sciences
Wellcome Trust (092545/Z/10/Z)
Biotechnology and Biological Sciences Research Council (BB/L00786X/1)
Wellcome Trust (103792/Z/14/Z)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)