Stem cells are necessary for the maintenance of many adult tissues. Signals within the stem cell microenvironment, or niche, regulate the self-renewal and differentiation capability of these cells. Misregulation of these signals through mutation or damage can lead to overgrowth or depletion of different stem cell pools. In this review, we focus on the Drosophila testis and ovary, both of which contain well-defined niches, as well as the mouse testis, which has become a more approachable stem cell system with recent technical advances. We discuss the signals that regulate gonadal stem cells in their niches, how these signals mediate self-renewal and differentiation under homeostatic conditions, and how stress, whether from mutations or damage, can cause changes in cell fate and drive stem cell competition.

Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit-Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in order for them to compete for occupancy in the niche. CySCs also require the Slit-Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of adherens junction components, suggesting that the two work together to balance CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT signaling, an important maintenance pathway for both germline and cyst stem cells in the testis. Our work indicates that Slit-Robo signaling affects stem cell function downstream of the JAK-STAT pathway by controlling the ability of stem cells to compete for occupancy in their niche.

SUMMARY Homeostasis in adult tissues depends on the precise regulation of stem cells and their surrounding microenvironments, or niches. Here, we show that the cell cycle inhibitor and tumor suppressor Retinoblastoma (RB) is a critical regulator of niche cells in the Drosophila testis. The testis contains a single niche, composed of somatic hub cells, that signals to adjacent germline and somatic stem cells. Hub cells are normally quiescent, but knockdown of the RB homolog Rbf in these cells causes them to proliferate and convert to somatic stem cells. Over time, mutant hub cell clusters enlarge and split apart, forming ectopic hubs surrounded by active stem cells. Furthermore, we show that Rbf’s ability to restrict niche number depends on the transcription factors E2F and Escargot and the adhesion molecule E-cadherin. Together this work reveals how precise modulation of niche cells, not only the stem cells they support, can drive regeneration and disease.