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来自冬眠器的iPSC为研究寒冷适应及其潜在的医学应用提供了平台

Jingxing Ou¹, John M Ball¹, Yizhao Luan²

¹Retinal Neurophysiology Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.

|March 27, 2018

概括

冬眠的哺乳动物具有耐寒的细胞机制. 研究人员在地松鼠诱导的多能干细胞 (iPSC) 中发现了增强人体细胞抗寒性和提高器官移植活力的途径.

科学领域:

细胞生物学
哺乳动物的冬眠
复原医学

背景情况:

冬眠的哺乳动物对极度寒冷 (低温) 具有显著的抵抗力, 保持细胞完整性而不会受伤.
这种耐寒的基本机制,特别是细胞骨的稳定性,尚未完全理解.
了解这些机制可能有重要的医学应用,包括器官移植和低温治疗.

研究的目的:

在冬眠中的哺乳动物中, 负责耐寒的细胞路径.
探索将这些适应寒冷的策略应用于包括人类在内的非冬眠物种的潜力.
评估冷藏器官用于移植的可行性.

主要方法:

从处于冬眠状态的哺乳动物 (地松鼠) 产生第一个诱导多能干细胞 (iPSC) 线.
人类和地松鼠iPSC衍生的神经元之间的冷反应的比较分析.
在人类iPSC神经元和老鼠视网膜组织中对已确定的细胞通路进行操纵.

主要成果:

在寒冷条件下观察到人类和地松鼠iPSC神经元之间的线粒体和蛋白质质量控制途径的不同反应.
在人类iPSC神经元中,寒冷诱导的线粒体应激,反应性氧物种 (ROS) 生产和溶酶体膜透,导致微管损伤.
操纵这些通路使人类iPSC神经元和老鼠视网膜具有微管冷稳定性,在暴露于冷气后保持功能. 冷藏的脏也显示出微管完整性的改善.

结论:

在研究寒冷适应机制方面,地松鼠的IPSC提供了有价值的模型.
针对特定的细胞通路可以提高非休眠细胞和组织的耐寒性.
这些发现显示出一种改善移植器官保存,延长其保质期的潜在策略.

关键词:

寒冷适应在地松鼠冬眠状态低温症诱导多能干细胞溶酶体膜通透性微管的冷稳定性线粒体器官存储视网膜

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