Modeling mammalian hibernation to improve intestinal cold preservation (PRJCA024863)

Static cold storage causes severe injuries for the intestine, which shortens the safe cold ischemic time and impedes the subsequent intestinal transplantation. Intriguingly, hibernating mammals, such as Syrian hamster, can protect organs from hypothermia, providing excellent models to study intestinal cold preservation. Here, we constructed the spatiotemporal hibernation atlas of Syrian hamster intestines and detected no evident injuries in torpid hamster intestines. Meanwhile, newly built hamster intestinal organoids could model intestinal hibernation by bearing cooling-rewarming stress, while their mouse counterparts failed to survive under cold stress. Furthermore, we demonstrated the importance of ACE2 in intestinal cold adaptation, as ACE2 was substantially upregulated in torpid hamster intestines and hamster organoids under cold stress, and its agonist, harpagoside, protected mouse organoids from cooling-rewarming stress and improved the cold preservation of the intestine and other organs. Altogether, our findings provide unique insights into improving organ cold preservation and examples for studying mammalian hibernation.