A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation. Issue 22 (3rd November 2018) - Nespolo, Roberto F.
Abstract: The small South American marsupial, Dromiciops gliroides, known as the missing link between the American and the Australian marsupials, is one of the few South American mammals known to hibernate. Expressing both daily torpor and seasonal hibernation, this species may provide crucial information about the mechanisms and the evolutionary origins of marsupial hibernation. Here, we compared torpid and active individuals, applying high‐throughput sequencing technologies (RNA‐seq) to profile gene expression in three D. gliroides tissues and determine whether hibernation induces tissue‐specific differential gene expression. We found 566 transcripts that were significantly up‐regulated during hibernation (369 in brain, 147 in liver and 50 in skeletal muscle) and 339 that were down‐regulated (225 in brain, 79 in liver and 35 in muscle). The proteins encoded by these differentially expressed genes orchestrate multiple metabolic changes during hibernation, such as inhibition of angiogenesis, prevention of muscle disuse atrophy, fuel switch from carbohydrate to lipid metabolism, protection against reactive oxygen species and repair of damaged DNA. According to the global enrichment analysis, brain cells seem to differentially regulate a complex array of biological functions (e.g., cold sensitivity, circadian perception, stress response), whereas liver and muscle cells prioritize fuel switch and heat production for rewarming. Interestingly, transcripts of thioredoxin‐interacting protein ( TXNIP ), a potent antioxidant, were significantly over‐expressed during torpor in all three tissues. These results suggest that marsupial hibernation is a controlled process where selected metabolic pathways show adaptive modulation that can help to maintain homeostasis and enhance cytoprotection in the hypometabolic state.