College of Life Sciences, Capital Normal University, Beijing 100048, China.
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Stem Cell Reports. 2022 Sep 13;17(9):1914-1923. doi: 10.1016/j.stemcr.2022.07.014. Epub 2022 Aug 18.
Germline stem cells (GSCs) are critical for the reproduction of an organism. The self-renewal and differentiation of GSCs must be tightly controlled to avoid uncontrolled stem cell proliferation or premature stem cell differentiation. However, how the self-renewal and differentiation of GSCs are properly controlled is not fully understood. Here, we find that the novel intrinsic factor Yun is required for female GSC maintenance in Drosophila. GSCs undergo precocious differentiation due to de-repression of differentiation factor Bam by defective BMP/Dpp signaling in the absence of yun. Mechanistically, Yun associates with and stabilizes Thickveins (Tkv), the type I receptor of Dpp/BMP signaling. Finally, ectopic expression of a constitutively active Tkv (Tkv) completely suppresses GSC loss caused by yun depletion. Collectively, these data demonstrate that Yun functions through Tkv to maintain GSC fate. Our results provide new insight into the regulatory mechanisms of how stem cell maintenance is properly controlled.
生殖干细胞 (GSCs) 对生物体的繁殖至关重要。GSCs 的自我更新和分化必须受到严格控制,以避免不受控制的干细胞增殖或过早的干细胞分化。然而,GSCs 的自我更新和分化是如何被适当控制的还不完全清楚。在这里,我们发现新型内在因子 Yun 在果蝇中对于雌性 GSC 的维持是必需的。由于 BMP/Dpp 信号的缺陷导致分化因子 Bam 的去抑制,GSCs 在没有 Yun 的情况下过早地分化。从机制上讲,Yun 与 Dpp/BMP 信号的 I 型受体 Thickveins (Tkv) 结合并稳定它。最后,组成型激活的 Tkv (Tkv) 的异位表达完全抑制了由 yun 耗竭引起的 GSC 丢失。总的来说,这些数据表明 Yun 通过 Tkv 发挥作用来维持 GSC 命运。我们的研究结果为如何适当控制干细胞维持的调控机制提供了新的见解。