The Drosophila testis harbors two types of stem cells: germ line stem cells (GSCs) and cyst stem cells (CySCs). Both stem cell types share a physical niche called the hub, located at the apical tip of the testis. The niche produces the JAK/STAT ligand Unpaired (Upd) and BMPs to maintain CySCs and GSCs, respectively. However, GSCs also require BMPs produced by CySCs, and as such CySCs are part of the niche for GSCs. Here we describe a role for another secreted ligand, Hedgehog (Hh), produced by niche cells, in the self-renewal of CySCs. Hh signaling cell-autonomously regulates CySC number and maintenance. The Hh and JAK/STAT pathways act independently and non-redundantly in CySC self-renewal. Finally, Hh signaling does not contribute to the niche function of CySCs, as Hh-sustained CySCs are unable to maintain GSCs in the absence of Stat92E. Therefore, the extended niche function of CySCs is solely attributable to JAK/STAT pathway function.

Summary Aging causes stem cell dysfunction as a result of extrinsic and intrinsic changes. Decreased function of the stem cell niche is an important contributor to this dysfunction. We use the Drosophila testis to investigate what factors maintain niche cells. The testis niche comprises quiescent “hub” cells and supports two mitotic stem cell pools: germline stem cells and somatic cyst stem cells (CySCs). We identify the cell-cycle-responsive Dp/E2f1 transcription factor as a crucial non-autonomous regulator required in CySCs to maintain hub cell quiescence. Dp/E2f1 inhibits local Activin ligands through production of the Activin antagonist Follistatin (Fs). Inactivation of Dp/E2f1 or Fs in CySCs or promoting Activin receptor signaling in hub cells causes transdifferentiation of hub cells into fully functional CySCs. This Activin-dependent communication between CySCs and hub regulates the physiological decay of the niche with age and demonstrates that hub cell quiescence results from signals from surrounding stem cells.

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