| Literature DB >> 29576452 |
Jingxing Ou1, John M Ball1, Yizhao Luan2, Tantai Zhao3, Kiyoharu J Miyagishima1, Yufeng Xu4, Huizhi Zhou5, Jinguo Chen5, Dana K Merriman6, Zhi Xie7, Barbara S Mallon8, Wei Li9.
Abstract
Hibernating mammals survive hypothermia (<10°C) without injury, a remarkable feat of cellular preservation that bears significance for potential medical applications. However, mechanisms imparting cold resistance, such as cytoskeleton stability, remain elusive. Using the first iPSC line from a hibernating mammal (13-lined ground squirrel), we uncovered cellular pathways critical for cold tolerance. Comparison between human and ground squirrel iPSC-derived neurons revealed differential mitochondrial and protein quality control responses to cold. In human iPSC-neurons, cold triggered mitochondrial stress, resulting in reactive oxygen species overproduction and lysosomal membrane permeabilization, contributing to microtubule destruction. Manipulations of these pathways endowed microtubule cold stability upon human iPSC-neurons and rat (a non-hibernator) retina, preserving its light responsiveness after prolonged cold exposure. Furthermore, these treatments significantly improved microtubule integrity in cold-stored kidneys, demonstrating the potential for prolonging shelf-life of organ transplants. Thus, ground squirrel iPSCs offer a unique platform for bringing cold-adaptive strategies from hibernators to humans in clinical applications. VIDEO ABSTRACT. Published by Elsevier Inc.Entities:
Keywords: cold adaptation; ground squirrel; hibernation; hypothermia; induced pluripotent stem cells; lysosomal membrane permeabilization; microtubule cold stability; mitochondria; organ storage; retina
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Year: 2018 PMID： 29576452 PMCID： PMC5935596 DOI： 10.1016/j.cell.2018.03.010
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582