Expression profiles in multiple tissues of WT and Nrf2-knockout mouse under space flight

Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS). After 31 days in the ISS, all flight mice returned safely to Earth. Transcriptome and metabolome analyses revealed that the stresses of space travel evoked ageing-like changes of plasma metabolites and activated the Nrf2 signaling pathway. Especially, Nrf2 was found to be important for maintaining homeostasis of white adipose tissues. This study opens approaches for future space research utilizing murine gene knockout-disease models, and provides insights into mitigating space-induced stresses that limit the further exploration of space by humans.

太空飞行可构建带有独特应激源的极端环境，但目前学界对人体如何应对这类应激因素仍缺乏深入认知。尽管在轨太空研究存在诸多难以逾越的局限，但借助基因敲除疾病模型小鼠（gene knockout-disease model mice）可突破其中部分限制。本研究探讨了应激防御通路的核心调控因子——核因子E2相关因子2（Nrf2）的缺失，对被运送至国际空间站（International Space Station, ISS）驻留的小鼠健康状况的影响。在国际空间站驻留31天后，所有航天组小鼠均安全返回地球。转录组（Transcriptome）与代谢组（Metabolome）分析结果显示，太空飞行引发的应激可诱发血浆代谢物出现衰老样变化，并激活Nrf2信号通路。尤为关键的是，研究发现Nrf2对维持白色脂肪组织的稳态具有重要作用。本研究为未来利用鼠类基因敲除疾病模型开展太空研究开辟了新路径，并为缓解制约人类深空探索的太空诱导应激提供了全新见解。