Singh Kanhaiya, Verma Priyanka, Srivastava Rajneesh, Rustagi Yashika, Kumar Manishekhar, Verma Sumit S, Mohanty Sujit, Beheshti Afshin, Warren Liz, Sen Chandan K
Center for Space Biomedicine at McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Indiana Center for Regenerative Medicine and Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
iScience. 2024 Nov 14;27(12):111382. doi: 10.1016/j.isci.2024.111382. eCollection 2024 Dec 20.
Genomic plasticity helps adapt to extreme environmental conditions. We tested the hypothesis that exposure to space environment (ESE) impacts the epigenome inducing genomic plasticity. Murine skin samples from the Rodent Research Reference Mission-1 were procured from the International Space Station (ISS) National Laboratory. Targeted RNA sequencing to test differential gene expression between the skin of ESE versus ground controls revealed upregulation of VEGF-mediated angiogenesis pathways secondary to promoter hypomethylation in responders. Methylome sequencing identified ESE-sensitive hypomethylated genes including developmental angiogenic genes , , and . Based on differentially expressed genes, the angiogenesis biofunction was enriched in responders. The induction of genomic plasticity in response to ESE, as reported herein, may be viewed as a mark of biological resilience that is evident in a minority of organisms, responders but not in non-responders, exposed to the same stressor. Inducible genomic plasticity may be implicated in natural resilience to ESE.
基因组可塑性有助于适应极端环境条件。我们检验了这样一个假设，即暴露于太空环境（ESE）会影响表观基因组，从而诱导基因组可塑性。从国际空间站（ISS）国家实验室获取了来自啮齿动物研究参考任务-1的小鼠皮肤样本。通过靶向RNA测序来检测ESE处理组与地面对照组皮肤之间的差异基因表达，结果显示，在有反应的小鼠中，由于启动子低甲基化，VEGF介导的血管生成途径上调。甲基化组测序确定了对ESE敏感的低甲基化基因，包括发育血管生成基因、和。基于差异表达基因，血管生成生物功能在有反应的小鼠中得到富集。如本文所述，对ESE作出反应而诱导的基因组可塑性，可被视为一种生物恢复力的标志，这种标志在少数暴露于相同应激源的生物体（有反应者而非无反应者）中很明显。可诱导的基因组可塑性可能与对ESE的自然恢复力有关。
