Regulation of niche cell plasticity in the Drosophila testis

Adult stem cells sustain tissue regeneration by responding to signals from their surrounding microenvironment or niche. Maintenance of stem cells and their niches is tightly regulated to prevent depletion or overgrowth of the stem cell pool. The Drosophila testis provides a uniquely accessible genetic system to study the regulation of niches in vivo. This niche consists of a cluster of quiescent somatic hub cells that signal to the attached germline and somatic cyst stem cells (CySCs). In several mammalian tissues, injury can cause non-dividing cells to re-enter the cell cycle and repair the tissue, but the mechanisms are not well understood. Recently, we have found that Drosophila testis hub cells respond to injury in a similar way. These quiescent cells start to proliferate upon genetic CySC ablation, followed by a change in cell identity. A subset of hub cells convert to somatic stem cells, thus replenishing the lost population. With age, however, these testes acquire ectopic hubs with active stem cells, leading to severe tissue disruption over time. Here I show that the cell cycle inhibitor and tumor suppressor Retinoblastoma homolog Rbf is required in the hub cells of the Drosophila testis to prevent their proliferation and conversion to CySCs. Additionally, continued Rbf loss causes hub cell clusters to split apart and form ectopic hubs, similar to those seen upon CySC ablation. These results suggest that cell cycle inhibitors are normally needed in terminally differentiated niche cells to ensure their proper maintenance. However, how hub cell plasticity is triggered upon injury to the testis still remained unknown. By activating or knocking down various signaling pathways in the hub I discovered that the EGF/MAPK pathway is sufficient to trigger hub cell proliferation and cell fate conversion. I further show that this pathway becomes activated in the hub upon CySC ablation, and is necessary to replenish lost somatic cyst stem cells after tissue damage. Altogether, this body of work demonstrates that the precise modulation of signals within niche cells, not just the stem cells they support, is necessary to drive tissue regeneration without disease progression