Regulation of somatic stem cell self-renewal by extrinsic factors in the Drosophila ovary

Adult stem cells play a pivotal role in maintaining tissue homeostasis due to their unique ability to self-renew and generate differentiated cells throughout an organism's lifetime. Somatic stem cells (SSCs) in the Drosophila ovary reside in the midway of the germarium and are responsible to generate epithelial cell-like follicle cells packaging differentiated germ cells into egg chambers and supporting oocyte growth and maturation. When the stem cell divides, one daughter cell remains anchored at the original position through E-cadherin-mediated cell adhesion and maintains the stem cell identity, while the other daughter cell moves away and differentiates into several distinct somatic follicle cell types. The control of the division rate and the stem cell identity depends on extrinsic signaling factors produced by the microenvironment, or niche. Two signaling pathways, Hedgehog and Wingless, have been previously demonstrated for their essential roles in regulation of SSC maintenance and proliferation. This work demonstrates that two additional extrinsic signals play roles in controlling SSC self-renewal in the Drosophila ovary.; Using the powerful Drosophila genetics, I have demonstrated that components of the BMP pathway are necessary for SSC maintenance. The SSCs defective in transmitting BMP signaling are lost from the germarium due to differentiation but not apoptosis. Additionally, when BMP signaling is specifically upregulated in SSC clones, using a new cell labeling and overexpression system, self-renewal ability is prolonged in comparison with wild-type clones. Further genetic analyses showed that hyperactive BMP signaling can substitute for loss of Wingless signaling but not Hedgehog signaling, suggesting that these signaling pathways work collaboratively to control SSC self-renewal.; Genetic mosaic analyses have also demonstrated that JAK-STAT signaling is required for controlling SSC self-renewal. However, in contrast to an essential role of BMP signaling in maintaining germline stem cells (GSCs), another type of stem cell in the Drosophila ovary, this pathway is dispensable for GSC self-renewal. Interestingly, overexpression of unpaired, the active ligand for the JAK-STAT pathway, not only enhances SSC lifespan but also slows down GSC differentiation.; The properties and regulatory circuits of the Drosophila ovarian SSCs are highly similar to embryonic stem cells and mammalian adult stem cells. Therefore, the knowledge gained from my studies may have direct implications for understanding regulation of stem cells in other systems, including humans.