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iPSCs from a Hibernator Provide a Platform for Studying Cold Adaptation and Its Potential Medical Applications.

Cell (2018-03-27)
Jingxing Ou, John M Ball, Yizhao Luan, Tantai Zhao, Kiyoharu J Miyagishima, Yufeng Xu, Huizhi Zhou, Jinguo Chen, Dana K Merriman, Zhi Xie, Barbara S Mallon, Wei Li

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.

Product Number
Product Description

Tetramethylrhodamine ethyl ester perchlorate, suitable for fluorescence, ≥90% (HPCE)
Anti-α-Tubulin−FITC antibody, Mouse monoclonal, clone DM1A, purified from hybridoma cell culture
OxyBlot Protein Oxidation Detection Kit, The OxyBlot Protein Oxidation Detection Kit provides the reagents to perform the immunoblot detection of carbonyl groups introduced into proteins by oxidative reactions with ozone or oxides of nitrogen or by metal catalyzed oxidation.
Anti-Tubulin Antibody, δ 2, Chemicon®, from rabbit