Stem cell-mediated tissue repair is a promising approach for many diseases. Mammalian intestine is an actively regenerating tissue such that epithelial cells are constantly shedding and underlying precursor cells are constantly replenishing the loss of cells. An imbalance of these processes will lead to intestinal diseases including inflammation and cancer. Mammalian intestinal stem cells (ISCs) are located in bases of crypts but at least two groups of cells have been cited as stem cells. Moreover, precursor cells in the transit amplifying zone can also proliferate. The involvement of multiple cell types makes it more difficult to examine tissue damage response in mammalian intestine. In adult Drosophila midgut, the ISCs are the only cells that can go through mitosis. By feeding pathogenic bacteria and stress inducing chemicals to adult flies, we demonstrate that Drosophila ISCs in the midgut can respond by increasing their division. The resulting enteroblasts, precursor cells for enterocytes and enteroendocrine cells, also differentiate faster to become cells resembling enterocyte lineage. These results are consistent with the idea that Drosophila midgut stem cells can respond to tissue damage induced by pathogens and initiate tissue repair. This system should allow molecular and genetic analyses of stem cell-mediated tissue repair.The gastrointestinal (GI) tract is not only for nutrient absorption but also a major site of interaction between the host and environmental pathogens (Backhed et al., 2005;Macdonald and Monteleone, 2005;Radtke and Clevers, 2005). In addition to the numerous microbes and chemicals ingested during daily food intake, the GI tract also houses billions of commensal bacteria, which play important symbiotic roles with the host. The complex interaction between intestinal cells and microbes, both commensal and ingested, is essential for the well being of the host. The epithelial lining of GI tract is essentially one to two-cell thick and the epithelium is constantly shedding cells due to aging or damage. Maintenance of the epithelial integrity requires replenishment of dead cells by proper division and differentiation of precursor cells (Crosnier et al., 2006;Scoville et al., 2008;Casali and Batlle, 2009). This tissue homeostasis is a highly regulated process, and Wnt, BMP and Notch signaling pathways have been implicated in mammalian intestinal cell maintenance and proliferation (Crosnier et al., 2006;Fodde and Brabletz, 2007;Nakamura et al., 2007). One possible mechanism for tissue homeostasis is perhaps based on adult stem cells. Intestinal stem cells (ISCs) divide asymmetrically in some way and give rise to progenitor cells, which in turn differentiate into various cell types in the intestine. Even thought ISCs in mouse intestine have been located to the base of each crypt, different markers have identified two groups of cells, namely +4 label retention cells and Lgr5-positive columnar base cells, as stem cells (Montgomery and Breault, 2008;Scoville et al., 2008;Casali and Batlle,...
