Physiological genomics最新文献

Physiological Genomics (PG) published its first issue in July 1999, with the goal of providing a forum for scientists to exchange ideas and scientific results related to the linkage between genetic information and physiological function. In this review, past and present editors reflect on PG's role in the scientific community, the founding of the journal and the historical context in which it was formed within the American Physiological Society (APS). The editors reflect on a critical conference that united physiologists and geneticists and their determination for APS to take the lead in integrating these communities. In the past 25 years, key technologies for linking genes to physiology including methods for DNA sequencing, connecting genotype with phenotype, and monitoring gene expression, metabolites, and microbiota have all been revolutionized, creating a dynamic scientific environment that has resulted in highly impactful research across a wide range of fields. As methods, technologies, and data analysis tools have developed, PG has been a consistent forum for sharing cutting-edge research on the latest advances in the rapidly evolving field of linking molecular data to physiological function. This article highlights the key technological advances related to the connection between genes and physiology. The contribution of the journal to the scientific community during the time periods of each of the five Editors-in-Chief are summarized, illuminating key technological approaches featured in PG and scientific questions that were addressed. The article ends with a look forward, describing what the authors anticipate for the future of PG.

Seasonal life-history events, such as migration, hibernation, and reproduction, depend on coordinated physiological changes. In vertebrates, a conserved thyroid hormone-signaling pathway in the hypothalamus is known to trigger many of these seasonal transitions. However, the broader processes and regulators modulating seasonal physiology are poorly defined. Recent research in Arctic ground squirrels (AGS, Urocitellus parryii) revealed that hypothalamic thyroid hormone signaling is activated, and markers of tanycytic remodeling are expressed in late hibernation in anticipation of springtime reproduction. We conducted RNA-sequencing on hypothalamic micropunches encompassing the arcuate nucleus, median eminence, pars tuberalis, and third ventricle in male and female AGS at early and late hibernation. We found substantial sex differences in the hypothalamic transcriptome across hibernation. Functional enrichment analysis of gene expression data revealed an upregulation of processes and pathways related to hormone transport and neurogenesis in females, whereas this was less apparent in males. Transcription factor binding site analysis of differentially expressed genes identified upstream regulators involved in glial cell differentiation, neuronal development, survival, and plasticity. Notably, many of the intersecting genes from these analyses were localized to specialized glial cells (tanycytes) lining the floor and walls of the third ventricle. Our findings support a model in which annual changes in gene expression rely on a progressive remodeling of tanycytes across hibernation. This remodeling may contribute to seasonal changes in neuronal plasticity and function of the hypothalamus, priming the brain in anticipation of shifting physiological demands upon hibernation termination.NEW & NOTEWORTHY We examine how the transcriptome of hypothalamic micropunches changes across the hibernation season. Our analyses uncover sex-specific changes to regulatory processes associated with hormone transport and neurogenesis. Genes linked to these processes and regulators are strongly localized to third ventricle tanycytes, consistent with the key role these cells play in regulating seasonal physiological changes. Our study supports that using sex as a biological variable is essential for understanding the mechanisms underlying seasonal life-history transitions.

Extracellular vesicles (EVs) are small, membrane-bound vesicles that transfer biological content through the extracellular environment. The role of EVs in energy metabolism has primarily focused on EV proteins and microRNAs, with less attention on the metabolic content of EVs. This exploratory study assessed changes in the EV metabolome in response to an arduous, 16-day military training exercise. Forty male soldiers (21 ± 2 yr, 24.8 ± 2.7 kg/m²) provided blood from which circulating EVs were isolated and completed assessments of body composition and lower body power on days 1 (PRE) and 16 (POST) of a mountain training exercise (MTX). Total daily energy expenditure during the MTX was 4,187 ± 519 kcal·day^-1. Fat mass (POST-PRE [95% confidence interval]: -0.9 [-1.3, -0.6] kg), lean body mass (-1.6 [-2.0, -1.2] kg), body fat percentage (-0.7 [-1.1, -0.3]%), and lower body power (-133 [-204, -63] W) decreased from PRE to POST (P < 0.05). Global metabolite profiling identified 81 metabolites from lipid (81%), energy (5%), cofactor and vitamin (5%), xenobiotic (4%), carbohydrate (2%), amino acid (1%), and nucleotide (1%) pathways in serum-derived EVs. After adjusting for EV concentration, 11 metabolites were different from PRE to POST (P < 0.05, Q < 0.20), with the largest increases in the oxidative stress-associated metabolites 5-oxoproline and benzoate. Changes in lean body mass were positively associated with changes in the energy metabolites citrate (ρ = 0.361, P = 0.022) and phosphate (ρ = 0.369, P = 0.019). Findings suggest that EV metabolites change in response to physiological stress and reflect increased oxidative stress, energy metabolism, and fatty acid metabolism, which may provide early indicators of stress adaptations relevant for optimizing training and sustaining military performance.NEW & NOTEWORTHY EV metabolites change in response to periods of increased metabolic demand, reflecting increased oxidative stress, energy metabolism, and fatty acid metabolism, and may be associated with changes in lean body mass. This exploratory study adds to the limited existing literature by highlighting the potential of EV-derived metabolites to provide insight into metabolic responses and their contribution to stress-induced metabolic adaptations.

The human microbiome is emerging as a key regulator of cancer biology, modulating tumor development, immune dynamics, and therapeutic responses across diverse malignancies. In this review, recent insights are synthesized regarding how microbial communities (bacterial, fungal, and viral) shape oncogenic signaling, immune checkpoint blockade (ICB) efficacy, and metabolic reprogramming in lung, pancreatic, colorectal, breast, cervical, melanoma, and gastric cancers. Mechanistic links between microbial metabolites, intratumoral colonization, and host immune phenotypes are highlighted proposing that the microbiome constitutes a programmable axis within the tumor immune-metabolic ecosystem. Drawing on multiomics integration and translational studies, a shift from associative profiling toward causal, spatially resolved, and intervention-ready frameworks is proposed. This perspective positions the microbiome not as a passive bystander, but as a coevolving participant in tumor progression and treatment response, with the potential to reshape diagnostics, prognostics, and therapeutic strategies in precision oncology.

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine miRNAs in pathways related to neuronal plasticity and autonomic regulation to construct a putative miRNA-target gene network involved in the development of neurogenic hypertension. We analyzed the dynamic correlations between the miRNAs and their putative targets to identify the regulatory interactions shifting between WKY and SHR. Comparing the results with previously published data in male SHR and WKY identified miRNA network dynamics specific to female SHR during hypertension development. Collectively, our results point to distinct rewiring of the miRNA regulatory networks governing angiotensin signaling and homeostasis, neuronal plasticity, and inflammatory processes contributing to the development of hypertension in female SHR.NEW & NOTEWORTHY Hypertension is the primary risk factor for cardiovascular complications and stroke. The microRNA expression changes in the central nervous system circuits driving hypertension development are understudied. Here, we show that microRNA-mediated regulatory networks are dynamically rewired during the development of high blood pressure phenotype by targeting key signaling pathways, neuronal plasticity, and inflammatory processes in a female rat model of human essential hypertension.

Excess glucocorticoids induce skeletal muscle myopathy by changing gene expression. Advanced age augments glucocorticoid-mediated muscle phenotypes, yet the transcriptional responses underlying those augmented phenotypes are unclear. The purpose of this study was to define the glucocorticoid-responsive transcriptome in young and aged muscle following both acute and more prolonged glucocorticoid treatment. Young (4-mo-old) or aged (24-mo-old) male mice were administered either an acute injection of dexamethasone (DEX) or vehicle or daily DEX or vehicle injections for 7 days. Muscles were harvested 6.5 h after the final or only injection. The tibialis anterior (TA) was selected for RNA sequencing analysis as DEX treatment lowered TA mass specifically in aged males. In silico analyses identified enriched pathways and transcription factors predicted to regulate DEX-sensitive genes. Acute DEX altered similar numbers of genes in young (950) versus aged males (913), although aged males had greater magnitudes of fold change. After 7 days of DEX treatment, aged muscle exhibited more DEGs compared with acute exposure (1,196 vs. 913), whereas young muscle exhibited fewer DEGs than after acute exposure (599 vs. 950). In aged males, glucocorticoid-sensitive genes were consistently enriched for growth regulatory processes across both time points, a pattern that was not evident in young males. Despite those age-associated transcriptional differences, the transcription factors predicted to regulate the glucocorticoid-sensitive genes were similar in young and aged males. These data expand our understanding into how aging modifies the transcriptional response to excess glucocorticoids in skeletal muscle.NEW & NOTEWORTHY Glucocorticoids promote mass loss in certain muscles with advanced age but not at younger ages. In a muscle whose mass is lost in response to elevated glucocorticoids only in advanced age in males, we show that glucocorticoids initiate a unique and exaggerated transcriptional profile after both acute exposure to the hormone and after prolonged treatment that is consistent with muscle atrophy. These findings expand our understanding of the effect primary aging has on glucocorticoid-induced atrophy in males.