A Novel Mechanism of Spermatogonia Death in Drosophila that Contributes to Tissue Homeostatis During Starvation.

[摘要] Tissues are maintained in a homeostatic state by balancing the constant loss of old cells with the continued production of new cells. Importantly, dysfunction of tissue homeostasis can lead to tumors or aging. Tissue homeostasis is constantly shifting process as it has to cope with environmental stress while maintaining the integrity of the tissue. For example, tissues often slow down their turnover and scale down tissue size to conserve energy when nutrient availability is limited. The role and behavior of resident stem cells in response to changes in the external environment have been heavily studied. In most of the tissue, stem cell division only constitutes a small fraction of total cell proliferation. Instead, the transit-amplifying cells account for the majority of proliferation. However, the contribution of these cells to shifting tissue homeostasis is less studied. The Drosophila melanogaster testis serves as an ideal model system to study the behavior of stem cells and transit-amplifying cells, as a result of its well-defined anatomy and the genetic tools. Recently, we demonstrated that elimination of transit-amplifying cells (i.e. spermatogonia) plays a critical role in maintaining the stem cell population during protein starvation. Inhibition of starvation-induced spermatogonial death leads to a loss of stem cells, impairment of tissue homeostasis, and failure to recover from starvation when nutrients are reintroduced. Regulation of transit-amplifying cells in the face of an environmental challenge is thus an essential process; however, it remains unclear how the death of spermatogonia leads to stem cell survival during protein starvation.In this dissertation, we identified a gene, spict, which is specifically expressed in differentiating somatic cells, and the corresponding Spict protein, which is stabilized in cyst cells surrounding the dying germ cells. We found that starvation-induced spermatogonial death was decreased in the spict mutant, resulting in a failure to maintain germline stem cells during prolonged protein starvation. We further demonstrated that dying spermatogonia are phagocytosed by neighboring somatic cyst cells, in which Spict protein is stabilized. Taken together, we propose that phagocytosis of dead spermatogonia, which is promoted by Spict, contributes to nutrient recycling and subsequent stem cell maintenance during protein starvation.

[发布机构] University of Michigan

[效力级别] tissue homeostasis

[关键词] cell death;tissue homeostasis;phagocytosis;Molecular;Cellular and Developmental Biology;Science;Cell and Developmental Biology