The regulated elimination of transit-amplifying cells preserves tissue homeostasis during protein starvation in Drosophila testis

Abstract

How tissues adapt to varying nutrient conditions is of fundamental importance for robust tissue homeostasis throughout the life of an organism, but the underlying mechanisms are poorly understood. Here, we show that Drosophila testis responds to protein starvation by eliminating transit-amplifying spermatogonia (SG) while maintaining a reduced pool of actively proliferating germline stem cells (GSCs). During protein starvation, SG die in a manner that is mediated by the apoptosis of somatic cyst cells (CCs) that encapsulate SG and regulate their development. Strikingly, GSCs cannot be maintained during protein starvation when CC-mediated SG death is inhibited, leading to an irreversible collapse of tissue homeostasis. We propose that the regulated elimination of transit-amplifying cells is essential to preserve stem cell function and tissue homeostasis during protein starvation.

spict, a cyst cell-specific gene, regulates starvation-induced spermatogonial cell death in the Drosophila testis

“…We noticed that Spict-mRFP extensively overlapped with Lysotracker staining (Fig. 3A,B, see below for detailed Spict localization), which we previously showed to mark dying SGs17. These observations prompted us to ask whether spict plays a role in SG death.…”

“…This argues that transit-amplifying cells, but not stem cells, may be a major point of regulation in response to changes in nutrient conditions. We have shown that starvation-induced SG death is triggered by apoptosis of CCs17. When CC death is blocked by inhibiting apoptosis, starvation-induced SG death was also blocked.…”

“…Recently, we reported that SG death dramatically increases in response to protein starvation17. The GSC population, however, is relatively well maintained even during a prolonged period of protein starvation.…”

“…The GSC population, however, is relatively well maintained even during a prolonged period of protein starvation. After an initial drop in GSC number from ~8/testis to ~6/testis after 3–6 days of starvation2, the remaining ~6 GSCs can be stably maintained for additional ~20 days while continuing to divide at an unchanged rate compared to fed conditions17. This argues that transit-amplifying cells, but not stem cells, may be a major point of regulation in response to changes in nutrient conditions.…”

“…When CC death is blocked by inhibiting apoptosis, starvation-induced SG death was also blocked. Concomitantly, testes failed to maintain their GSC population, leading to collapsed tissue homeostasis and compromised ability to recover upon reintroduction of nutrients17. These results led us to speculate that SG death upon protein starvation serves as a mechanism to protect GSCs in two ways.…”