The adult Drosophila testis lacks a mechanism to replenish missing niche cells.

The adult Drosophila testis contains a well-defined niche created by a cluster of hub cells, which secrete signals that maintain adjacent germline stem cells and somatic cyst stem cells (CySCs). Hub cells are normally quiescent in adult flies but can exit quiescence, delaminate from the hub and convert into CySCs after ablation of all CySCs. The opposite event, CySC conversion into hub cells, was proposed to occur under physiological conditions, but the frequency of this event is debated. Here, to probe further the question of whether or not hub cells can be regenerated, we developed methods to genetically ablate some or all hub cells. Surprisingly, when flies were allowed to recover from ablation, the missing hub cells were not replaced. Hub cells did not exit quiescence after partial ablation of hub cells, and labeled cells from outside the hub did not enter the hub during or after ablation. Despite its ability to exit quiescence in response to CySC ablation, we conclude that the hub in the adult Drosophila testis does not have a mechanism to replenish missing hub cells.

Niche signaling promotes stem cell survival in the Drosophila testis via the JAK-STAT target DIAP1.

Tissue-specific stem cells are thought to resist environmental insults better than their differentiating progeny, but this resistance varies from one tissue to another, and the underlying mechanisms are not well-understood. Here, we use the Drosophila testis as a model system to study the regulation of cell death within an intact niche. This niche contains sperm-producing germline stem cells (GSCs) and accompanying somatic cyst stem cells (or CySCs). Although many signals are known to promote stem cell self-renewal in this tissue, including the highly conserved JAK-STAT pathway, the response of these stem cells to potential death-inducing signals, and factors promoting stem cell survival, have not been characterized. Here we find that both GSCs and CySCs resist cell death better than their differentiating progeny, under normal laboratory conditions and in response to potential death-inducing stimuli such as irradiation or starvation. To ask what might be promoting stem cell survival, we characterized the role of the anti-apoptotic gene Drosophila inhibitor of apoptosis 1 (diap1) in testis stem cells. DIAP1 protein is enriched in the GSCs and CySCs and is a JAK-STAT target. diap1 is necessary for survival of both GSCs and CySCs, and ectopic up-regulation of DIAP1 in somatic cyst cells is sufficient to non-autonomously rescue stress-induced cell death in adjacent differentiating germ cells (spermatogonia). Altogether, our results show that niche signals can promote stem cell survival by up-regulation of highly conserved anti-apoptotic proteins, and suggest that this strategy may underlie the ability of stem cells to resist death more generally.

Conversion of quiescent niche cells to somatic stem cells causes ectopic niche formation in the Drosophila testis.

Adult stem cells reside in specialized regulatory microenvironments, or niches, where local signals ensure stem cell maintenance. The Drosophila testis contains a well-characterized niche wherein signals from postmitotic hub cells promote maintenance of adjacent germline stem cells and somatic cyst stem cells (CySCs). Hub cells were considered to be terminally differentiated; here, we show that they can give rise to CySCs. Genetic ablation of CySCs triggers hub cells to transiently exit quiescence, delaminate from the hub, and convert into functional CySCs. Ectopic Cyclin D-Cdk4 expression in hub cells is also sufficient to trigger their conversion into CySCs. In both cases, this conversion causes the formation of multiple ectopic niches over time. Therefore, our work provides a model for understanding how oncogenic mutations in quiescent niche cells could promote loss of quiescence, changes in cell fate, and aberrant niche expansion.