Integrative Transcription Start Site Analysis and Physiological Phenotyping Reveal Torpor-specific Expressions in Mouse Skeletal Muscle
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE117937 | GEO | 2018/08/01
REPOSITORIES: GEO
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Project description:Harsh environments enforce the expression of behavioural, morphological, physiological, and reproductive rejoinders, including torpor. Here we study the morphological, cellular, and molecular alterations in torpor architype in the colonial urochordate Botrylloides aff. leachii by employing whole organism Transmission electron (TEM) and light microscope observations, RNA sequencing, real-time polymerase chain reaction (qPCR) quantification of selected genes, and immunoloc- alization of WNT, SMAD and SOX2 gene expressions. On the morphological level, torpor starts with gradual regression of all zooids and buds which leaves the colony surviving as condensed vasculature remnants that may be ‘aroused’ to regenerate fully functional colonies upon changes in the environment. Simultaneously, we observed altered distributions of hemolymph cell types. Phagocytes doubled in number, while the number of morula cells declined by half. In addition, two new circulating cell types were observed, multi-nucleated and bacteria-bearing cells. RNA sequencing technology revealed marked differences in gene expression between different organism compartments and states: active zooids and ampullae, and between mid-torpor and naive colonies, or naive and torpid colonies. Gene Ontology term enrichment analyses further showed disparate biological processes. In torpid colonies, we observed overall 233 up regulated genes. These genes included NR4A2, EGR1, MUC5AC, HMCN2 and. Also, 27 transcription factors were upregulated in torpid colonies including ELK1, HDAC3, RBMX, MAZ, STAT1, STAT4 and STAT6. Interestingly, genes involved in developmental processes such as SPIRE1, RHOA, SOX11, WNT5A and SNX18 were also upregulated in torpid colonies. We further validated the dysregulation of 22 genes during torpor by utilizing qPCR. Immunohistochemistry of representative genes from three signaling pathways revealed high expression of these genes in circulated cells along torpor. WNT agonist administration resulted in early arousal from torpor in 80% of the torpid colonies while in active colonies WNT agonist triggered the torpor state. Abovementioned results thus connote unique transcriptome landscapes associated with Botrylloides leachii torpor.
2023-03-02 | GSE226392 | GEO
Project description:Integrative Transcription Start Site Analysis and Physiological Phenotyping Reveal Torpor-specific Expressions in Mouse Skeletal Muscle
| PRJNA483766 | ENA
Project description:Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise, and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (> 24 hours) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic brown adipose tissue. Single-nucleus RNA-sequencing of POA neurons reveals TRPM2 as an ultrasound-sensitive ion channel, the knockdown of which suppresses UIH. We also demonstrate that UIH is feasible in a non-torpid animal, the rat. Our findings establish UIH as a promising technology for the noninvasive and safe induction of a torpor-like state. To investigate the mechanism of ultrasound-induced neuronal activation, we applied ultrasound stimulation in hypothalamic preoptic area region and performed single-nuclei RNA sequencing in the ultrasound stimulated neurons (US+) and neurons without ultrasound stimulation (US-). In our sn-RNAseq analysis, we examined the association between the expression of neuronal activation markers (or IEGs) and ion channels, as well as neuron types.
2023-03-29 | GSE228180 | GEO
Project description: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.
2023-07-30 | GSE239559 | GEO
Project description:Comparative transcriptomics of the garden dormouse hypothalamus during early torpor, late torpor and interbout arousal of hibernation
2023-11-13 | GSE207494 | GEO
Project description:Differential gene expression in a wide range of tissues including brown adipose tissue (BAT), liver, heart, hypothalamus, and skeletal muscle in hibernating arctic ground squirrels during multiple stages in torpor-arousal cycles compared to non-hibernating (post-reproductive) animals with illumina beadarray technology. Arctic Ground Squirrels were sampled at four stages of hibernation: early arousal denoted as EA (1-2 hrs after Tb cross 30¡C, n=4), late arousal denoted as LA (7-8 hrs after Tb cross 30¡C, n=4), early torpor denoted as ET (10-20% of torpid episode, n=4) and late torpor denoted as LT (80-90% of torpid episode, n=5), where Tb is the body temperature and the length of torpid episode is estimated from the previous torpor bout. Post-reproductive animals denoted as PR (n=7) were used as non-hibernating control. Five tissue types: brown adipose tissue (BAT), liver, heart, hypothalamus, and skeletal muscle were hybridized on two customized 700-gene beadarray platforms: 1A and 2A on 96-sample Illumina ArrayMatrix. The data of a pilot study involving brown adipose tissue (BAT), liver, and skeletal muscle on 16-sample Illumina BeadChip denoted as 16chip are also included in this series.
2010-07-01 | E-GEOD-5414 | biostudies-arrayexpress
Project description:The advent of endothermy more than a hundred million years ago is thought to have been a defining feature of mammalian and avian evolution, achieved through continuous fine-tuned homeostatic regulation of core body temperature and metabolism. However, when challenged by food deprivation or harsh environmental conditions, many mammalian species initiate adaptive energy-conserving survival strategies, including torpor and hibernation, during which their core body temperature decreases far below its homeostatic setpoint. How homeothermic mammals initiate and regulate these extraordinary hypothermic states remains largely unknown. Here, we discover that entry into mouse torpor, a fasting-induced state with greatly decreased metabolic rate and body temperature as low as 20°C, is regulated by a population of neurons in the preoptic area of the hypothalamus. We show that re-stimulation of neurons activated during a previous bout of torpor is sufficient to initiate torpor, even in animals that are not calorically restricted. We localize these torpor-regulating neurons to the anteroventral medial and lateral preoptic area and molecularly identify a population of glutamatergic Adcyap1+ neurons whose activity accurately determines when calorically-restricted animals naturally initiate and exit torpor, and whose inhibition disrupts the natural process of torpor entry, maintenance and arousal. Taken together, we discover a specific hypothalamic neuronal subpopulation in the mouse brain that serves as a core regulator of torpor. This work forms the basis for future explorations of mechanisms and circuitry regulating extreme hypothermic and hypometabolic states, enabling genetic access to monitor, initiate, manipulate and study these ancient adaptations of homeotherm biology.
2020-04-30 | GSE149344 | GEO
Project description:Neurons that regulate mouse torpor
| PRJNA628074 | ENA
Project description:We hypothesised that induction of a torpor-like state would confer a radioprotective effect given the evidence that hibernation extends survival times in irradiated squirrels compared to active controls. To test this hypothesis, a torpor-like state was induced in zebrafish using melatonin treatment and cold temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing of mRNA extracted from the GIT. A systems level analysis was performed on the transcriptomic data to characterise the cellular phenotypes in radiation, torpor, and torpor+radiation groups. The results revealed that melatonin and cold temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, damage to the central nervous system and cell cycle arrest. This stress response was attenuated in the torpor+radiation group by an increase in biosynthesis, proliferation, cell survival signals and expression of genes involved in protection against the adverse effects of radiation, particularly in neurons, suggesting a radioprotective effect conferred by a torpor state. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure.
2021-04-28 | GSE169522 | GEO
Project description:Bats are the only mammals capable of self-powered flying. Many bat species hibernate in winter. A reversible control of cerebral activities is critical for bats to accommodate a repeated torpor-arousal cycle during hibernation. Little is known about the molecular mechanism that regulates neuronal activities in torpid bats. In this study, brain proteins were fractionated and compared between torpid and active Rhinolophus ferrumequinum bats.
2017-05-11 | PXD005158 | Pride