Blood transcriptomics mirror regulatory mechanisms during hibernation

Hibernation enables many species of the mammalian kingdom to overcome periods of harsh environmental conditions. During this physically inactive state metabolic rate and body temperature are drastically downregulated, thereby reducing energy requirements (torpor) also over shorter time periods. Since blood cells reflect the organism's current condition, it was suggested that transcriptomic alterations in blood cells mirror the torpor-associated physiological state. Transcriptomics on blood cells of torpid and non-torpid Djungarian hamsters and QIAGEN Ingenuity Pathway Analysis (IPA) revealed key target molecules (TMIPA), which were subjected to a comparative literature analysis on transcriptomic alterations during torpor/hibernation in other mammals. Gene expression similarities were identified in 148 TMIPA during torpor nadir among various organs and phylogenetically different mammalian species. Based on TMIPA, IPA network analyses corresponded with described inhibitions of basic cellular mechanisms and immune system-associated processes in torpid mammals. Moreover, protection against damage of heart, kidney, and liver was deduced from this gene expression pattern in blood cells. This study shows that blood cell transcriptomics can reflect the general physiological state during torpor nadir. Furthermore, the understanding of molecular processes for torpor initiation and organ preservation may have beneficial implications for humans in extremely challenging environments, such as in medical intensive care units and in space. Overall design: All 36 SP-acclimated hamsters were observed to express spontaneous daily torpor, which is a drop of Tb <32 °C for at least 30 minutes. Over different sampling times, 18 hamsters were hypothermic (HT) and expressed torpor and the other 18 hamsters did not and served as normothermic controls (NT). During torpor entry (ZT01) samples were obtained from 6 NT and 5 HT animals; during torpor nadir/ or mid torpor (ZT04) samples from 4 NT and 5 HT animals; during torpor arousal (ZT07) samples from 4 NT and 4 HT animals, and post-torpor (ZT16) from 4 NT and 4 HT animals. For sampling, hamsters were sacrificed by carbon dioxide inhalation inside their home cage at an age of 32 ± 4 weeks. 5 hamsters didn't perform torpor for their whole life served as overall control. Each sample is the blood sample of one animal.