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.

由于外在和内在的变化，衰老会导致干细胞功能障碍。干细胞生态位的功能下降是导致这种功能障碍的重要原因。我们使用果蝇睾丸来研究维持生态位细胞的因素。睾丸生态位包括静止的“中枢”细胞并支持两个有丝分裂干细胞库：生殖系干细胞和体细胞囊肿干细胞 (CySCs)。我们将细胞周期响应性 Dp/E2f1 转录因子确定为 CySC 维持中枢细胞静止所需的关键非自主调节因子。Dp/E2f1 通过产生激活素拮抗剂 Follistatin (Fs) 抑制局部激活素配体。CySC 中 Dp/E2f1 或 Fs 的失活或促进中枢细胞中的激活素受体信号传导导致中枢细胞转分化为功能齐全的 CySC。CySCs 和中枢之间的这种依赖于激活素的通讯调节生态位随年龄增长的生理衰退，并证明中枢细胞静止是由周围干细胞的信号引起的。