Puerta David, Rivera-Martín Sara, Fragoso-Luna Adrián, Strome Susan, Crittenden Sarah L, Kimble Judith, Pérez-Martín José
Instituto de Biomedicina de Valencia (CSIC), Valencia, Spain.
Instituto de Biología Funcional y Genómica (CSIC), Salamanca, Spain.
Sci Adv. 2025 May 30;11(22):eadu8572. doi: 10.1126/sciadv.adu8572.
Originally known for its function in the cell cycle, the anaphase-promoting complex/cyclosome (APC/C) also plays a crucial role in regulating differentiation and maintaining cell identity. However, the mechanisms by which APC/C mediates developmental processes are not fully understood. In this study, we show that APC/C and its activator FZR-1 regulate the chromatin regulators MES-4 and MES-3. These proteins are part of histone methylation complexes essential for maintaining germline stem cell (GSC) identity in the germ line of . APC/C facilitates the degradation of MES-4 and MES-3 when GSCs transition toward differentiating into oocytes. The activity of APC/C is restricted by the Notch signaling pathway provided by the distal tip cell, which is responsible for maintaining the stemness of the GSC pool. This negative regulation enables the accumulation of MES-3 and MES-4 in GSCs, offering an additional component by which niche activity modulates the germ line.
后期促进复合体/细胞周期体(APC/C)最初因在细胞周期中的功能而为人所知,它在调节分化和维持细胞特性方面也起着关键作用。然而,APC/C介导发育过程的机制尚未完全明确。在本研究中,我们表明APC/C及其激活因子FZR-1调节染色质调节因子MES-4和MES-3。这些蛋白质是组蛋白甲基化复合体的一部分,对于在线虫生殖系中维持生殖系干细胞(GSC)特性至关重要。当生殖系干细胞向分化为卵母细胞转变时,APC/C促进MES-4和MES-3的降解。APC/C的活性受到远端末梢细胞提供的Notch信号通路的限制,远端末梢细胞负责维持生殖系干细胞库的干性。这种负调控使得MES-3和MES-4在生殖系干细胞中积累,为微环境活性调节生殖系提供了一个额外的组成部分。