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

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. Targeted DamID with RNA pol II and Sox21a. Pol II: two conditions (ISCs/Ebs, esg driver; ECs, myo driver), two replicates per protein per condition; Sox21a: one condition (ISCs/EBs, esg driver), three replicates.