Physiological genomics最新文献

{"title":"Transcriptional response of the heart to vagus nerve stimulation.","authors":"Daniel O Kellett, Qadeer Aziz, Jonathan D Humphries, Alla Korsak, Alice Braga, Ana Gutierrez Del Arroyo, Marilena Crescente, Andrew Tinker, Gareth L Ackland, Alexander V Gourine","doi":"10.6084/m9.figshare.24449590","DOIUrl":"10.6084/m9.figshare.24449590","url":null,"abstract":"<p><p>Heart failure is a major clinical problem, with treatments involving medication, devices, and emerging neuromodulation therapies such as vagus nerve stimulation (VNS). Considering the ongoing interest in using VNS to treat cardiovascular disease it is important to understand the genetic and molecular changes developing in the heart in response to this form of autonomic neuromodulation. This experimental animal (rat) study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity using an optogenetic approach. Vagal preganglionic neurons in the dorsal motor nucleus of the vagus nerve were genetically targeted to express light-sensitive chimeric channelrhodopsin variant ChIEF, and stimulated using light. RNA sequencing of left ventricular myocardium identified 294 differentially expressed genes (DEGs, false discovery rate <0.05). Qiagen Ingenuity Pathway Analysis (IPA) highlighted 118 canonical pathways that were significantly modulated by vagal activity, of which 14 had a z-score of ≥2/≤-2, including EIF-2, IL-2, Integrin, and NFAT-regulated cardiac hypertrophy. IPA revealed the effect of efferent vagus stimulation on protein synthesis, autophagy, fibrosis, autonomic signalling, inflammation, and hypertrophy. IPA further predicted that the identified DEGs were the targets of 50 upstream regulators, including transcription factors (e.g., MYC, NRF1) and microRNAs (e.g., miR-335-3p, miR-338-3p). These data demonstrate that the vagus nerve has a major impact on myocardial expression of genes involved in regulation of key biological pathways. The transcriptional response of the ventricular myocardium induced by stimulation of vagal efferents is consistent with the beneficial effect of maintained/increased vagal activity on the heart.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen induction of immune cells in the mammary glands during pregnancy.","authors":"Karen Yamaguchi, Jun Nakayama, Tomofumi Yamamoto, Kentaro Semba, Tatsuo Shirota, Yusuke Yamamoto","doi":"10.1152/physiolgenomics.00098.2023","DOIUrl":"10.1152/physiolgenomics.00098.2023","url":null,"abstract":"<p><p>The mammary glands are dynamic tissues affected by pregnancy-related hormones during the pregnancy-lactation cycle. Collagen production and its dynamics are essential to the remodeling of the mammary glands. Alterations of the mammary microenvironment and stromal cells during the pregnancy-lactation cycle are important for understanding the physiology of the mammary glands and the development of breast tumors. In this study, we performed an evaluation of collagen dynamics in the mammary fat pad during the pregnancy-lactation cycle. Reanalysis of single-cell RNA-sequencing (scRNA-Seq) data showed the ectopic collagen expression in the immune cells and cell-cell interactions for collagens with single-cell resolution. The scRNA-Seq data showed that type I and type III collagen were produced not only by stromal fibroblasts but also by lymphoid and myeloid cell types in the pregnancy phase. Furthermore, the total cell-cell interaction score for collagen interactions was dramatically increased in the pregnancy tissue. The data presented in this study provide evidence that immune cells contribute, at least in part, to mammary collagen dynamics. Our findings suggest that immune cells, including lymphoid and myeloid cells, might be supportive members of the extracellular matrix orchestration in the pregnancy-lactation cycle of the mammary glands.<b>NEW & NOTEWORTHY</b> Our study evaluated mammary gland collagen dynamics during the pregnancy-lactation cycle using single-cell RNA-sequencing data. We found ectopic collagen expression in immune cells and an increase in collagen interactions during pregnancy. Type I and type III collagen were produced by lymphoid, myeloid, and stromal fibroblast cells during pregnancy. These findings suggest that immune cells, including lymphoid and myeloid cells, play a crucial role in supporting the extracellular matrix in mammary glands during pregnancy-lactation cycles.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PANoptosis in vascular smooth muscle cells regulated by TNF-α/IL-1β can be a new target for alleviating the progression of abdominal aortic aneurysm.","authors":"Kun Li, Mingyang Wei, Dongbin Zhang, Shuiting Zhai, Hongzhi Liu","doi":"10.1152/physiolgenomics.00053.2023","DOIUrl":"10.1152/physiolgenomics.00053.2023","url":null,"abstract":"<p><p>PANoptosis is an inflammatory programmed cell death (PCD) regulated by multifaceted PANoptosome complexes with major features of pyroptosis, apoptosis, and/or necroptosis that cannot be accounted for by any of these PCD pathways alone. The aim of this study was to investigate the role of PANoptosis on the occurrence and development of abdominal aortic aneurysm (AAA). Clinical samples of patients with AAA, angiotensin II (ANG II)-induced AAA mouse model, and ANG II-induced vascular smooth muscle cells (VSMCs) in vitro model were used for investigation on PANoptosis features. The expressions of ZBP1, AIM2, and other markers related to pyroptosis, apoptosis, and necroptosis elevated obviously in aortic wall tissues of patients with AAA, mice with AAA, and ANG II-treated VSMCs. ANG II treatment increased inflammatory cytokines levels in VSMCs. The stimulation of tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β) alone promoted VSMCs death, and the effect of TNF-α combined with IL-1β is more obvious. The expressions of ZBP1, AIM2, and related markers of pyroptosis, apoptosis, and necroptosis were increased by TNF-α and IL-1β combined treatment. Inhibition of TNF-α and/or IL-1β in mice with AAA improved the AAA pathology, reduced the loss of VSMCs, decreased the expression of ZBP1 and AIM2, and markers associated with pyroptosis, apoptosis, and necroptosis. PANoptosis features were observed in aortic wall tissues of patients with AAA, mice with AAA, and ANG II-treated VSMCs. The inhibition of TNF-α and IL-1β can alleviate PANoptosis in mice with AAA, which provides a new strategy for the prevention and treatment of AAA.<b>NEW & NOTEWORTHY</b> Early detection, diagnosis, and treatment are very important to improve the quality of life and prognosis of patients with abdominal aortic aneurysm (AAA). Based on the findings of apoptosis, necroptosis, and pyroptosis (PANoptosis) in AAA clinical samples, this study further explored the molecular mechanism in vivo and in vitro. Specifically, inhibition of tumor necrosis factor-α and interleukin-1β can reduce PANoptosis in vascular smooth muscle cell and thus alleviate the process of AAA.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomics analysis of allergen-induced inflammatory gene expression in the Four-Core Genotype mouse model.","authors":"Carolyn Damilola Ekpruke, Rachel Alford, Dustin Rousselle, Maksat Babayev, Shikha Sharma, Sarah Commodore, Aaron Buechlein, Douglas B Rusch, Patricia Silveyra","doi":"10.1152/physiolgenomics.00112.2023","DOIUrl":"10.1152/physiolgenomics.00112.2023","url":null,"abstract":"<p><p>Sex differences in allergic inflammation have been reported, but the mechanisms underlying these differences remain unknown. Contributions of both sex hormones and sex-related genes to these mechanisms have been previously suggested in clinical and animal studies. Here, Four-Core Genotypes (FCG) mouse model was used to study the inflammatory response to house dust mite (HDM) challenge and identify differentially expressed genes (DEGs) and regulatory pathways in lung tissue. Briefly, adult mice (8-10 wk old) of the FCG (XXM, XXF, XYM, XYF) were challenged intranasally with 25 μg of HDM or vehicle (PBS-control group) 5 days/wk for 5 wk (<i>n</i> = 3/10 group). At 72 h after the last exposure, we analyzed the eosinophils and neutrophils in the bronchoalveolar lavage (BAL) of FCG mice. We extracted lung tissue and determined DEGs using Templated Oligo-Sequencing (TempO-Seq). DEG analysis was performed using the DESeq2 package and gene enrichment analysis was done using Ingenuity Pathway Analysis. A total of 2,863 DEGs were identified in the FCG. Results revealed increased eosinophilia and neutrophilia in the HDM-treated group with the most significantly expressed genes in XYF phenotype and a predominant effect of female hormones vs. chromosomes. Regardless of the sex hormones, mice with female chromosomes had more downregulated genes in the HDM group but this was reversed in the control group. Interestingly, genes associated with inflammatory responses were overrepresented in the XXM and XYF genotypes treated with HDM. Sex hormones and chromosomes contribute to inflammatory responses to HDM challenge, with female hormones exerting a predominant effect mediated by inflammatory DEGs.<b>NEW & NOTEWORTHY</b> Gene expression profiling helps to provide deep insight into the global view of disease-related mechanisms and responses to therapy. Using the Four-Core Genotype mouse model, our findings revealed the influence of sex hormones and sex chromosomes in the gene expression of lungs exposed to an aeroallergen (House Dust Mite) and identified sex-specific pathways to better understand sex disparities associated with allergic airway inflammation.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic changes in glomeruli in response to a high salt challenge in the Dahl SS rat.","authors":"Marharyta Semenikhina, Daria V Lysikova, Denisha R Spires, Mark Domondon, Krisztian Stadler, Oleg Palygin, Daria V Ilatovskaya","doi":"10.1152/physiolgenomics.00075.2023","DOIUrl":"10.1152/physiolgenomics.00075.2023","url":null,"abstract":"<p><p>Salt sensitivity impacts a significant portion of the population and is an important contributor to the development of chronic kidney disease. One of the significant early predictors of salt-induced damage is albuminuria, which reflects the deterioration of the renal filtration barrier: the glomerulus. Despite significant research efforts, there is still a gap in knowledge regarding the molecular mechanisms and signaling networks contributing to instigating and/or perpetuating salt-induced glomerular injury. To address this gap, we used 8-wk-old male Dahl salt-sensitive rats fed a normal-salt diet (0.4% NaCl) or challenged with a high-salt diet (4% NaCl) for 3 wk. At the end of the protocol, a pure fraction of renal glomeruli obtained by differential sieving was used for next-generation RNA sequencing and comprehensive semi-automatic transcriptomic data analyses, which revealed 149 differentially expressed genes (107 and 42 genes were downregulated and upregulated, respectively). Furthermore, a combination of predictive gene correlation networks and computational bioinformatic analyses revealed pathways impacted by a high salt dietary challenge, including renal metabolism, mitochondrial function, apoptotic signaling and fibrosis, cell cycle, inflammatory and immune responses, circadian clock, cytoskeletal organization, G protein-coupled receptor signaling, and calcium transport. In conclusion, we report here novel transcriptomic interactions and corresponding predicted pathways affecting glomeruli under salt-induced stress.<b>NEW & NOTEWORTHY</b> Our study demonstrated novel pathways affecting glomeruli under stress induced by dietary salt. Predictive gene correlation networks and bioinformatic semi-automatic analysis revealed changes in the pathways relevant to mitochondrial function, inflammatory, apoptotic/fibrotic processes, and cell calcium transport.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenylate cyclase 3: a potential genetic link between obesity and major depressive disorder.","authors":"Mackenzie Fitzpatrick, Leah C Solberg Woods","doi":"10.1152/physiolgenomics.00056.2023","DOIUrl":"10.1152/physiolgenomics.00056.2023","url":null,"abstract":"<p><p>Obesity and major depressive disorder (MDD) are both significant health issues that have been increasing in prevalence and are associated with multiple comorbidities. Obesity and MDD have been shown to be bidirectionally associated, and they are both influenced by genetics and environmental factors. However, the molecular mechanisms that link these two diseases are not yet fully understood. It is possible that these diseases are connected through the actions of the cAMP/protein kinase A (PKA) pathway. Within this pathway, adenylate cyclase 3 (<i>Adcy3</i>) has emerged as a key player in both obesity and MDD. Numerous genetic variants in <i>Adcy3</i> have been identified in humans in association with obesity. Rodent knockout studies have also validated the importance of this gene for energy homeostasis. Furthermore, <i>Adcy3</i> has been identified as a top candidate gene and even a potential blood biomarker for MDD. <i>Adcy3</i> and the cAMP/PKA pathway may therefore serve as an important genetic and functional link between these two diseases. In this mini-review, we discuss the role of both <i>Adcy3</i> and the cAMP/PKA pathway, including specific genetic mutations, in both diseases. Understanding the role that <i>Adcy3</i> mutations play in obesity and MDD could open the door for precision medicine approaches and treatments for both diseases that target this gene.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and metabolomics profiles in patients with chronic stable angina and acute coronary syndrome.","authors":"Adilah F Ahmad, Jose A Caparrós-Martin, Nicola Gray, Samantha Lodge, Julien Wist, Silvia Lee, Fergal O'Gara, Girish Dwivedi, Natalie C Ward","doi":"10.1152/physiolgenomics.00072.2023","DOIUrl":"10.1152/physiolgenomics.00072.2023","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in patients with chronic stable angina (CSA) and acute coronary syndrome (ACS) compared with healthy controls. Bacterial alpha diversity in stool from patients with ACS or CSA was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units (OTUs) assigned to commensal taxa differentiating patients with ACS from healthy controls at both baseline and follow-up. Patients with CSA and ACS had significantly higher levels of trimethylamine <i>N</i>-oxide compared with healthy controls (CSA: 0.032 ± 0.023 mmol/L, <i>P</i> < 0.01 vs. healthy, and ACS: 0.032 ± 0.023 mmol/L, <i>P</i> = 0.02 vs. healthy, respectively). Patients with ACS had reduced levels of propionate and butyrate (119 ± 4 vs. 139 ± 5.1 µM, <i>P</i> = 0.001, and 14 ± 4.3 vs. 23.5 ± 8.1 µM, <i>P</i> < 0.001, respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs. 1834 ± 45.8 ng/mL, <i>P</i> < 0.0001) and sCD163 levels (457.3 ± 31.8 vs. 326.8 ± 20.7 ng/mL, <i>P</i> = 0.001), compared with healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in patients with CSA and ACS compared with healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD. Future time course studies in patients to observe temporal changes and subsequent associations with gut microbiome composition are required to provide insight into how these are affected by transient changes following an acute coronary event.<b>NEW & NOTEWORTHY</b> The study found discriminative microorganisms differentiating patients with acute coronary syndrome (ACS) from healthy controls. In addition, reduced levels of certain bacterial metabolites and elevated sCD14 and sCD163 were observed in patients with ACS compared with healthy controls. Furthermore, modified small molecule metabolomic and lipidomic signatures were found in both patient groups. Although it is not known whether these differences in profiles are associated with disease development and/or progression, the findings provide exciting options for potential new disease-related mechanism(s) and associated therapeutic target(s).</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring myometrial microenvironment changes at the single-cell level from nonpregnant to term pregnant states.","authors":"Kaiyuan Ji, Junmin Zhong, Long Cui, Xiaodi Wang, Li-Na Chen, Bolun Wen, Fan Yang, Wenfeng Deng, Xiuyu Pan, Lele Wang, Junjie Bao, YunShan Chen, Huishu Liu","doi":"10.1152/physiolgenomics.00067.2023","DOIUrl":"10.1152/physiolgenomics.00067.2023","url":null,"abstract":"<p><p>The microenvironment and cell populations within the myometrium play crucial roles in maintaining uterine structural integrity and protecting the fetus during pregnancy. However, the specific changes occurring at the single-cell level in the human myometrium between nonpregnant (NP) and term pregnant (TP) states remain unexplored. In this study, we used single-cell RNA sequencing (scRNA-Seq) and spatial transcriptomics (ST) to construct a transcriptomic atlas of individual cells in the myometrium of NP and TP women. Integrated analysis of scRNA-Seq and ST data revealed spatially distinct transcriptional characteristics and examined cell-to-cell communication patterns based on ligand-receptor interactions. We identified and categorized 87,845 high-quality individual cells into 12 populations from scRNA-Seq data of 12 human myometrium tissues. Our findings demonstrated alterations in the proportions of five subpopulations of smooth muscle cells in TP. Moreover, an increase in monocytic cells, particularly M2 macrophages, was observed in TP myometrium samples, suggesting their involvement in the anti-inflammatory response. This study provides unprecedented single-cell resolution of the NP and TP myometrium, offering new insights into myometrial remodeling during pregnancy.<b>NEW & NOTEWORTHY</b> Using single-cell RNA sequencing and spatial transcriptomics, the myometrium was examined at the single-cell level during pregnancy. We identified spatially distinct cell populations and observed alterations in smooth muscle cells and increased M2 macrophages in term pregnant women. These findings offer unprecedented insights into myometrial remodeling and the anti-inflammatory response during pregnancy. The study advances our understanding of pregnancy-related myometrial changes.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The uterine secretory cycle: recurring physiology of endometrial outputs that setup the uterine luminal microenvironment.","authors":"Kasey M Schalich, Prasanthi P Koganti, Juan M Castillo, Olivia M Reiff, Soon Hon Cheong, Vimal Selvaraj","doi":"10.1152/physiolgenomics.00035.2023","DOIUrl":"10.1152/physiolgenomics.00035.2023","url":null,"abstract":"<p><p>Conserved in female reproduction across all mammalian species is the estrous cycle and its regulation by the hypothalamic-pituitary-gonadal (HPG) axis, a collective of intersected hormonal events that are crucial for ensuring uterine fertility. Nonetheless, knowledge of the direct mediators that synchronously shape the uterine microenvironment for successive yet distinct events, such as the transit of sperm and support for progressive stages of preimplantation embryo development, remain principally deficient. Toward understanding the timed endometrial outputs that permit luminal events as directed by the estrous cycle, we used Bovidae as a model system to uniquely surface sample and study temporal shifts to in vivo endometrial transcripts that encode for proteins destined to be secreted. The results revealed the full quantitative profile of endometrial components that shape the uterine luminal microenvironment at distinct phases of the estrous cycle (estrus, metestrus, diestrus, and proestrus). In interpreting this comprehensive log of stage-specific endometrial secretions, we define the \"uterine secretory cycle\" and extract a predictive understanding of recurring physiological actions regulated within the uterine lumen in anticipation of sperm and preimplantation embryonic stages. This repetitive microenvironmental preparedness to sequentially provide operative support was a stable intrinsic framework, with only limited responses to sperm or embryos if encountered in the lumen within the cyclic time period. In uncovering the secretory cycle and unraveling realistic biological processes, we present novel foundational knowledge of terminal effectors controlled by the HPG axis to direct a recurring sequence of vital functions within the uterine lumen.<b>NEW & NOTEWORTHY</b> This study unravels the recurring sequence of changes within the uterus that supports vital functions (sperm transit and development of preimplantation embryonic stages) during the reproductive cycle in female Ruminantia. These data present new systems knowledge in uterine reproductive physiology crucial for setting up in vitro biomimicry and artificial environments for assisted reproduction technologies for a range of mammalian species.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10203797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous nonsense mutation in the tuftelin 1 gene is associated with abnormal hair appearance and amelioration of glucose and lipid metabolism in the rat.","authors":"Jan Šilhavý, Petr Mlejnek, Miroslava Šimáková, František Liška, Hana Malínská, Irena Marková, Martina Hüttl, Denisa Miklánková, Dita Mušálková, Viktor Stránecký, Stanislav Kmoch, Eva Sticová, Marek Vrbacký, Tomáš Mráček, Michal Pravenec","doi":"10.1152/physiolgenomics.00084.2023","DOIUrl":"10.1152/physiolgenomics.00084.2023","url":null,"abstract":"<p><p>Recently, we have identified a recessive mutation, an abnormal coat appearance in the BXH6 strain, a member of the HXB/BXH set of recombinant inbred (RI) strains. The RI strains were derived from the spontaneously hypertensive rat (SHR) and Brown Norway rat (BN-<i>Lx</i>) progenitors. Whole genome sequencing of the mutant rats identified the 195875980 G/A mutation in the tuftelin 1 (<i>Tuft1</i>) gene on chromosome 2, which resulted in a premature stop codon. Compared with wild-type BXH6 rats, BXH6-<i>Tuft1</i> mutant rats exhibited lower body weight due to reduced visceral fat and ectopic fat accumulation in the liver and heart. Reduced adiposity was associated with decreased serum glucose and insulin and increased insulin-stimulated glycogenesis in skeletal muscle. In addition, mutant rats had lower serum monocyte chemoattractant protein-1 and leptin levels, indicative of reduced inflammation. Analysis of the liver proteome identified differentially expressed proteins from fatty acid metabolism and β-oxidation, peroxisomes, carbohydrate metabolism, inflammation, and proteasome pathways. These results provide evidence for the important role of the <i>Tuft1</i> gene in the regulation of lipid and glucose metabolism and suggest underlying molecular mechanisms.<b>NEW & NOTEWORTHY</b> A new spontaneous mutation, abnormal hair appearance in the rat, has been identified as a nonfunctional tuftelin 1 (<i>Tuft1</i>) gene. The pleiotropic effects of this mutation regulate glucose and lipid metabolism. Analysis of the liver proteome revealed possible molecular mechanisms for the metabolic effects of the <i>Tuft1</i> gene.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89719282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}