Department of Biochemistry, University of Washington, Seattle, United States.
Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, United States.
Elife. 2017 Sep 19;6:e27842. doi: 10.7554/eLife.27842.
Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify and mTOR homologue, as important regulators of GSC quiescence following exposure to ionizing radiation. is required for entry in quiescence, while is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of .
衰老的干细胞失去了适当响应损伤和再生其所在组织的能力。在这里,我们利用生殖干细胞 (GSCs) 能够在低剂量电离辐射 (IR) 下存活的能力作为成体干细胞损伤的模型,并在衰老的 GSCs 中发现了一个再生缺陷:虽然衰老的 GSCs 在暴露于 IR 后存活下来,但它们不能及时重新进入细胞周期并再生生殖系。从机制上讲,我们确定 和 mTOR 同源物 是电离辐射暴露后 GSC 静止的重要调节剂。 对于进入静止状态是必需的,而 对于细胞周期再进入是必不可少的。重要的是,我们进一步表明,IR 后生殖系干细胞缺乏再生可以通过 缺失来挽救。