衰老和疾病中的干细胞损失与核变形有关。然而,细胞核形状如何影响干细胞稳态的了解甚少。我们使用果蝇生殖系干细胞调查了这种联系,由于这些干细胞的存活受到核层功能障碍的影响,广泛的蛋白质网络,排列在内核膜上并赋予细胞核形状。为了诱导生殖干细胞的核畸变,我们使用GAL4-UAS系统来增加永久性法尼基化核层蛋白的表达,Kugelkern,核生长的速率限制因素。我们表明,Kugelkern水平升高会导致种系干细胞严重的核畸变,包括核膜和核层的广泛增厚和分叶,以及内部核隔室的改变。尽管有这些变化,种系干细胞数量,扩散,女性的生育能力得以保留,即使是女性的年龄。总的来说,这些数据表明,核结构的破坏不会导致种系干细胞存活或稳态的失败,揭示核变形并不总是促进干细胞损失。
Stem cell loss in aging and disease is associated with nuclear deformation. Yet, how nuclear shape influences stem cell homeostasis is poorly understood. We investigated this connection using Drosophila germline stem cells, as survival of these stem cells is compromised by dysfunction of the nuclear lamina, the extensive protein network that lines the inner nuclear membrane and gives shape to the nucleus. To induce nuclear distortion in germline stem cells, we used the GAL4-UAS system to increase expression of the permanently farnesylated nuclear lamina protein, Kugelkern, a rate limiting factor for nuclear growth. We show that elevated Kugelkern levels cause severe nuclear distortion in germline stem cells, including extensive thickening and lobulation of the nuclear envelope and nuclear lamina, as well as alteration of internal nuclear compartments. Despite these changes, germline stem cell number, proliferation, and female fertility are preserved, even as females age. Collectively, these data demonstrate that disruption of nuclear architecture does not cause a failure of germline stem cell survival or homeostasis, revealing that nuclear deformation does not invariably promote stem cell loss.