Abstract
Stem cells are maintained in a specialized microenvironment called niche but the nature of stem cell niche remains poorly defined in many systems. Here we demonstrate that intestinal epithelium-derived BMP serves as a niche signal for intestinal stem cell (ISC) self-renewal in Drosophila adult midgut. We find that BMP signaling is asymmetric between ISC and its differentiated daughter cell. Two BMP ligands, Dpp and Gbb, are produced by enterocytes and act in conjunction to promote ISC self-renewal by antagonizing Notch signaling. Furthermore, the basement membrane-associated type IV collagens regulate ISC self-renewal by confining higher BMP signaling to ISCs. The employment of gut epithelia as a niche for stem cell self-renewal may provide a mechanism for direct communication between the niche and the environment, allowing niche signal production and stem cell number to be fine-tuned in response to various physiological and pathological stimuli. DOI: http://dx.doi.org/10.7554/eLife.01857.001.
Highlights
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 still not fully understood
We found that inactivation of bone morphogenetic proteins (BMPs) signaling in adult midgut precursor cells by knocking down either type I or type II receptor blocked DSS- or bleomycin-induced intestinal stem cell (ISC) proliferation, as indicated by the diminished mitotic cells recognized by staining with an anti-phospho-histone 3 (PH3) antibody (Figure 1B)
BMP signaling regulates ISC proliferation because reduction in BMP pathway activity results in ISC overproliferation (Guo et al, 2013; Li et al, 2013b), which is in line with a growth inhibitory role of BMP signaling in mammalian intestines (Haramis et al, 2004; He et al, 2004)
Summary
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 still not fully understood. Drosophila posterior midgut contains self-renewing stem cells located adjacent to the basement membrane (BM) of the midgut epithelium (Figure 1A; Micchelli and Perrimon, 2006; Ohlstein and Spradling, 2006). These intestine stem cells (ISCs) undergo cell division and asymmetric fate determination to produce a renewed ISC and an enteroblast (EB). Fate determination between the two ISC daughter cells is regulated by N signaling (Micchelli and Perrimon, 2006; Ohlstein and Spradling, 2006, 2007; Bardin et al, 2010). How asymmetric N signaling between two ISC daughter cells is
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