A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation

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.

Southernmost records of Dromiciops gliroides: extending its distribution beyond the Valdivian rainforest

“…The ecological patterns of D. gliroides are quite consistent across the Valdivian rainforest, showing similar home ranges, body condition and population densities among sites of Argentina and Chile (Fontúrbel et al 2012). However, we do not know how D. gliroides may respond to environmental conditions southwards of the Valdivian temperate rainforest, where there are larger daily and seasonal temperature fluctuations, lower rainfall, and colder nights that may trigger hibernation responses (Nespolo et al 2018), narrowing their activity patterns. Also, we found differences in the forest composition.…”

Waking the sleeping dragon: gene expression profiling reveals adaptive strategies of the hibernating reptile Pogona vitticeps

“…These periods of euthermia allow animals to rewarm and replenish gene and protein products; processes that are virtually halted during torpor [1]. Two decades of molecular studies of hibernation have focused on mammals, such as bears and squirrels [2][3][4][5][6][7][8], and recently marsupials [9], with little consideration of hibernation in reptiles. Debate surrounds the use of the word 'hibernation' in reptiles, with the thought that the lack of active body temperature regulation and inconsistent use of torpor necessitates an alternative term, i.e.…”

Bringing nature back: using hibernation to reboot organ preservation

“…A potential Nature‐inspired solution for this could be treatments that suppress cold‐sensing by organ explants. New data from an mRNA transcriptomic analysis of the liver from a hibernating marsupial species suggest that active controls are exerted on the cold‐sensing transmembrane receptor channel, TRPM8, to silence its function in the membrane when animals enter torpor . The regulation of TRPM8 and its effects on cold‐sensing has also been implicated in a variety of other hibernators .…”