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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 48; pp. 12218 - 12223
• Main Authors: Doupé, David P., Marshall, Owen J., Dayton, Hannah, Brand, Andrea H., Perrimon, Norbert
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27-11-2018
• Subjects: Animals; Autocrine signalling; Biological Sciences; Cell growth; Cell proliferation; Cells (biology); Digital archives; Drosophila; Drosophila - cytology; Drosophila - physiology; Drosophila Proteins - metabolism; Gene expression; Homeostasis; Insulin; Intestines - cytology; Ligands; Midgut; Paracrine signalling; Progenitor cells; Regulators; Regulatory sequences; Signal Transduction; Stem Cell Niche; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transcription factors; microenvironment; stem cells; niche; insulin; epithelial homeostasis
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1719169115

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.