In adult life, many organs rely on stem cells to maintain their integrity by replenishing lost cells during tissue homeostasis and regeneration, yet the regulatory mechanisms that control stem cell proliferation, self-renewal and differentiation are not fully understood.We are studying these mechanisms using Drosophila adult midgut as a model system.We find that the Hippo tumor suppressor pathway restricts intestinal stem cell (ISC) proliferation through both cell autonomous and non-cell autonomous mechanisms.We also find that injury can promote Hedgehog signaling in midgut precursor cells, which in turn stimulates ISC proliferation through the JAK-STAT pathway.In addition, we have demonstrated that epithelium-derived BMP serve as a niche signal to promote ISC self-renewal in the midgut.We find that Decapentaplegic (Dpp) and Glass-bottom boat (Gbb) are produced by enterocytes with Dpp exhibiting basal enrichment, and that Dpp and Gbb act in conjunction to promote ISC fate by antagonizing Notch-mediated differentiation.Extracellular matrix proteins at the basement membrane regulate ISC self-renewal by controlling the range of BMP signaling.Furthermore, epithelial damage can increase BMP production and signaling,leading to increased ISC population and rapid midgut regeneration.The employment of midgut epithelium as a niche for stem cell self-renewal may provide a mechanism for direct communication between the stem cell niche and the environment, allowing niche signal production and stem cell pool size to be fine-tuned in response to various physiological and pathological stimuli.