Powell Amanda M, Williams Anna E, Ables Elizabeth T
Department of Biology, East Carolina University, Greenville, NC, 27858.
Current address: Biochemistry, Cell and Developmental Biology Graduate Program, Emory University, Atlanta, GA, 30322.
bioRxiv. 2025 Mar 13:2025.03.10.642432. doi: 10.1101/2025.03.10.642432.
Many tissue-resident stem cells are retained through asymmetric cell division, a process that ensures stem cell self-renewal through each mitotic cell cycle. Asymmetric organelle distribution has been proposed as a mechanism by which stem cells are marked for long-term retention; however, it is not clear whether biased organelle localization is a cause or an effect of asymmetric division. In females, an endoplasmic reticulum-like organelle called the fusome is continually regenerated in germline stem cells (GSCs) and associated with GSC division. Here, we report that the β-importin Tnpo-SR is essential for fusome regeneration. Depletion of disrupts cytoskeletal organization during interphase and nuclear membrane remodeling during mitosis. Tnpo-SR does not localize to microtubules, centrosomes, or the fusome, suggesting that its role in maintaining these processes is indirect. Despite this, we find that restoring fusome morphogenesis in -depleted GSCs is sufficient to rescue GSC maintenance and cell cycle progression. We conclude that Tnpo-SR functionally fusome regeneration to cell cycle progression, supporting the model that asymmetric rebuilding of fusome promotes maintenance of GSC identity and niche retention.
许多组织驻留干细胞通过不对称细胞分裂得以保留,这一过程可确保干细胞在每个有丝分裂细胞周期中实现自我更新。不对称细胞器分布被认为是干细胞长期保留的一种机制;然而,尚不清楚细胞器的偏向性定位是不对称分裂的原因还是结果。在雌性个体中,一种名为融合体的内质网样细胞器在生殖系干细胞(GSCs)中持续再生,并与GSC分裂相关。在此,我们报告β-输入蛋白Tnpo-SR对融合体再生至关重要。其缺失会破坏间期的细胞骨架组织以及有丝分裂期间的核膜重塑。Tnpo-SR并不定位于微管、中心体或融合体,这表明其在维持这些过程中的作用是间接的。尽管如此,我们发现恢复缺失Tnpo-SR的GSCs中的融合体形态发生足以挽救GSC的维持和细胞周期进程。我们得出结论,Tnpo-SR在功能上将融合体再生与细胞周期进程联系起来,支持了融合体的不对称重建促进GSC身份维持和生态位保留的模型。