Physiological genomics最新文献

{"title":"Molecular insights into human soleus muscle atrophy development: long-term dry immersion effects on the transcriptomic profile and posttranslational signaling.","authors":"Roman O Bokov, Kristina A Sharlo, Natalia A Vilchinskaya, Sergey A Tyganov, Olga V Turtikova, Sergey V Rozhkov, Ruslan M Deviatiiarov, Oleg A Gusev, Elena S Tomilovskaya, Boris S Shenkman, Oleg I Orlov","doi":"10.1152/physiolgenomics.00196.2024","DOIUrl":"10.1152/physiolgenomics.00196.2024","url":null,"abstract":"<p><p>Muscle disuse results in complex signaling alterations followed by structural and functional changes, such as atrophy, force decrease, and slow-to-fast fiber-type shift. Little is known about human skeletal muscle signaling alterations under long-term muscle disuse. In this study, we describe the effects of 21-day dry immersion on human postural soleus muscle. We performed both transcriptomic analysis and Western blots to describe the states of the key signaling pathways regulating soleus muscle fiber size, fiber type, and metabolism. Twenty-one-day dry immersion resulted in both slow-type and fast-type myofibers atrophy, downregulation of rRNA content, and mTOR signaling. Twenty-one-day dry immersion also leads to slow-to-fast fiber-type and gene expression shift, upregulation of p-eEF2, p-CaMKII, p-ACC content and downregulation of NFATc1 nuclear content. It also caused massive gene expression alterations associated with calcium signaling, cytoskeletal parameters, and downregulated mitochondrial signaling (including fusion, fission, and marker of mitochondrial density).<b>NEW & NOTEWORTHY</b> The main findings of our study are as follows: <i>1</i>) The soleus slow fibers atrophy after 21-day dry immersion (DI) does not exceed that after 7-day DI; <i>2</i>) The soleus ubiquitin ligases expression after 21-day DI returns to its initial level; <i>3</i>) The soleus slow fibers atrophy after 21-day DI is accompanied by a mitochondrial apparatus structural markers decrease; <i>4</i>) The soleus fibers signaling pathways restructuring process during 21-day DI is carried out in a complex manner.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"357-382"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615994","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":"Divergent multiomic acute exercise responses reveal the impact of sex as a biological variable.","authors":"Kaleen M Lavin, Samia M O'Bryan, Khyatiben V Pathak, Krystine Garcia-Mansfield, Zachary A Graham, Jeremy S McAdam, Devin J Drummer, Margaret B Bell, Christian J Kelley, Manoel E Lixandrão, Brandon Peoples, Regina S Seay, Anakaren R Torres, Rebecca Reiman, Eric Alsop, Elizabeth Hutchins, Anna Bonfitto, Jerry Antone, Joanna Palade, Kendall Van Keuren-Jensen, Matthew J Huentelman, Patrick Pirrotte, Timothy Broderick, Marcas M Bamman","doi":"10.1152/physiolgenomics.00055.2024","DOIUrl":"10.1152/physiolgenomics.00055.2024","url":null,"abstract":"<p><p>The majority of exercise physiology research has been conducted in males, resulting in a skewed biological representation of how exercise impacts the physiological system. Extrapolating male-centric physiological findings to females is not universally appropriate and may even be detrimental. Thus, addressing this imbalance and taking into consideration sex as a biological variable is mandatory for optimization of precision exercise interventions and/or regimens. Our present analysis focused on establishing multiomic profiles in young, exercise-naïve males (<i>n</i> = 23) and females (<i>n</i> = 17) at rest and following acute exercise. Sex differences were characterized at baseline and following exercise using skeletal muscle and extracellular vesicle transcriptomics, whole blood methylomics, and serum metabolomics. Sex-by-time analysis of the acute exercise response revealed notable overlap, and divergent molecular responses between males and females. An exploratory comparison of two combined exercise regimens [high-intensity tactical training (HITT) and traditional (TRAD)] was then performed using singular value decomposition, revealing latent data structures that suggest a complex dose-by-sex interaction response to exercise. These findings lay the groundwork for an understanding of key differences in responses to acute exercise exposure between sexes. This may be leveraged in designing optimal training strategies, understanding common and divergent molecular interplay guiding exercise responses, and elucidating the role of sex hormones and/or other sex-specific attributes in responses to acute and chronic exercise.<b>NEW & NOTEWORTHY</b> This study examined methylomics, transcriptomics, and metabolomics in circulation and/or skeletal muscle of young, healthy, exercise-naïve males and females before and after exposure to either traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found an overlapping yet considerably sex-divergent response in the molecular mechanisms activated by exercise. These findings may provide insight into optimal training strategies for adaptation when considering sex as a biological variable.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"321-342"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516404","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":"Evidence of a novel gene locus <i>ARHGAP44</i> for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study.","authors":"Siyu Wang, Petra Lenzini, Bharat Thyagarajan, Joseph H Lee, Badri N Vardarajan, Anatoli Yashin, Iva Miljkovic, E Warwick Daw, Shiow J Lin, Gary J Patti, Michael R Brent, Joseph M Zmuda, Thomas T Perls, Kaare Christensen, Michael A Province, Ping An","doi":"10.1152/physiolgenomics.00137.2024","DOIUrl":"10.1152/physiolgenomics.00137.2024","url":null,"abstract":"<p><p>Glycated hemoglobin A1c (HbA1c) indicates average glucose levels over 3 mo and is associated with insulin resistance and type 2 diabetes (T2D). Longitudinal change in circulating HbA1c (ΔHbA1c) is also associated with aging processes, cognitive performance, and mortality. We analyzed ΔHbA1c in 1,886 nondiabetic Europeans from the Long Life Family Study (LLFS) to uncover gene loci influencing ΔHbA1c. Using growth curve modeling adjusted for multiple covariates, we derived ΔHbA1c and conducted linkage-guided sequence analysis. Our genome-wide linkage scan identified a significant locus on <i>17p12</i>. In-depth analysis revealed a gene locus <i>ARHGAP44</i> (rs56340929, explaining 27% of the linkage peak) that was significantly associated with ΔHbA1c. Interestingly, RNA transcription of <i>ARHGAP44</i> was also significantly associated with ΔHbA1c in the LLFS, and this discovery was replicable on the gene locus level in the Framingham Offspring Study (FOS). Taking together, we successfully identified a novel gene locus <i>ARHGAP44</i> for ΔHbA1c in family members without T2D. Further follow-up studies using longitudinal omics data in large independent cohorts are warranted.<b>NEW & NOTEWORTHY</b> HbA1c is clinically used in T2D diagnosis and monitoring. Its longitudinal change (ΔHbA1c) is associated with T2D-related aging processes and mortality. Targeted association tests under significant linkage peaks in extended families permit identification of unique gene loci. We uncovered a novel gene locus <i>ARHGAP44</i> for ΔHbA1c with gene-level validations from the FOS and RNAseq data in the LLFS. The finding provides genetically informed biological insight into mechanistic inference of glycemia/HbA1c homeostasis and potential T2D pathophysiology.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"293-298"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528174","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":"Novel effects of reverse transcriptase inhibitor supplementation in skeletal muscle of old mice.","authors":"Shelby C Osburn, Meghan E Smith, Devin Wahl, Thomas J LaRocca","doi":"10.1152/physiolgenomics.00115.2024","DOIUrl":"10.1152/physiolgenomics.00115.2024","url":null,"abstract":"<p><p>Aging is the primary risk factor for the development of many chronic diseases, including dementias, cardiovascular disease, and diabetes. There is significant interest in identifying novel \"geroprotective\" agents, including by repurposing existing drugs, but such treatments may affect organ systems differently. One current example is the nucleoside reverse transcriptase inhibitor 3TC, which has been increasingly studied as a potential gerotherapeutic. Recent data suggest that 3TC may reduce inflammation and improve cognitive function in older mice; however, the effects of 3TC on other tissues in aged animals are less well characterized. Here, we use transcriptomics (RNA-seq) and targeted metabolomics to investigate the influence of 3TC supplementation on skeletal muscle in older mice. We show that 3TC <i>1</i>) does not overtly affect muscle mass or functional/health markers, <i>2</i>) largely reverses age-related changes in gene expression and metabolite signatures, and <i>3</i>) is potentially beneficial for mitochondrial function in old animals via increases in antioxidant enzymes and decreases in mitochondrial reactive oxygen species. Collectively, our results suggest that, in addition to its protective effects in other tissues, 3TC supplementation does not have adverse effects in aged muscle and may even protect muscle/mitochondrial health in this context.<b>NEW & NOTEWORTHY</b> Recent studies suggest that the nucleoside reverse transcriptase inhibitor 3TC may improve brain health and cognitive function in old mice, but its effects on other aging tissues have not been comprehensively studied. This is the first study to use a multiomics approach to investigate the effects of 3TC treatment on skeletal muscle of old mice. The results suggest that 3TC reverses age-related transcriptomic and metabolite signatures and is potentially beneficial for mitochondrial function in aged muscle.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"308-320"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586497","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":"From castaways to discoveries: unveiling treasures in skin RNAseq using a novel multidimensional data processing workflow including infection-host dynamics.","authors":"Disha Bhargava, Alec Labadie, Rebecca L Hanson-Rios-Stutz, Austin Goodyke, Ella M Moses, Akansha S Das, Sophie Vanderweele, Janelle V Lemon, Taylor W Cook, David Pearson, Joseph M Redinger, Adam J Caulfield, Rosemary Olivero, Kate Foster, Kurt Ashack, Surender Rajasekaran, Caleb P Bupp, Timothy J Triche, Connie M Krawczyk, Dave Chesla, Matthew D Sims, Nicholas L Hartog, Jeremy W Prokop","doi":"10.1152/physiolgenomics.00093.2024","DOIUrl":"10.1152/physiolgenomics.00093.2024","url":null,"abstract":"<p><p>Defining physiology and methods to measure biological mechanisms is essential. Extensive datasets such as RNA sequencing are used with little analysis of the knowledge gained from the various methodologies. Within this work, we have processed publicly available NCBI RNAseq datasets using a combination of bioinformatics tools for the largest physiological organ, the skin. In many datasets, we identify the quality of the sample, human transcript mapping, the sex of each sample, foreign RNA from bacteria/viruses/protists, and the presence of B/T-cell immune repertoire. Processing 8,274 samples from 132 different experiments for skin samples identifies common flora of skin with elevation of protists (such as <i>Leishmania</i>), bacteria (<i>Staphylococcus</i>, <i>Cutibacterium acnes</i>), and viruses [Human alphaherpesvirus (HSV), Human papillomavirus (HPV)] that may be involved in physiological differences. We observed samples with the Heilongjiang tick virus, human T-cell leukemia virus type I, and equine infectious anemia virus that likely play pathological roles in physiology. Integrating the various biomarkers identified five ideal datasets for skin pathologies that elucidated a novel correlation between the normal skin flora bacterium <i>Bacillus megaterium</i> with major histocompatibility complex (MHC) regulation and the immune repertoire clonal expansion, particularly in patients with hidradenitis suppurativa. Finally, we show that in multiple independent experiments, biological sex is associated with multiple sex chromosome gene differences, highlighting the importance of future work in studying sex differences in skin. Data integrations and multidimensional data mapping are critical for physiological omics advancements, and this work highlights the exciting ability to apply these tools to skin physiology.<b>NEW & NOTEWORTHY</b> Complex bioinformatics mapping to skin RNA sequencing datasets can simultaneously map biological sex, skin-specific genes, bacteria, viruses, protists, and the acquired immune response. The integration of these datasets elucidated bacterial signatures from common skin flora while identifying novel insights on <i>Bacillus megaterium</i> in the acquired immune response and novel viral signatures for Heilongjiang tick virus and equine infectious anemia virus.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"343-356"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615993","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":"Differences in the bacterial communities along the intestinal tract of juvenile channel (<i>Ictalurus punctatus</i>) and hybrid (<i>I. punctatus</i>× <i>I. furcatus</i>) catfish.","authors":"Caitlin E Older, Penelope M Goodman, J Grant Reifers, Fernando Y Yamamoto","doi":"10.1152/physiolgenomics.00008.2025","DOIUrl":"10.1152/physiolgenomics.00008.2025","url":null,"abstract":"<p><p>Hybrid catfish (<i>Ictalurus punctatus</i> × <i>I. furcatus</i>) is the preferred catfish for US aquaculture due to the heterosis exhibited in many production traits. Improvements in fry production protocols have enabled widespread adoption of these hybrids, with producers using management practices optimized for channel catfish. Research to consider differences, outside of production traits, which may exist between hybrids and their parent species is lacking. Utilizing management practices specifically designed for hybrids may improve production efficiency. The gut microbiome plays critical roles in host development and health and, thus, is relevant to production. In the present study, the microbiota in the anterior, middle, and posterior segments of the intestinal tract were compared between channel and hybrid catfish using high-throughput 16S rRNA gene sequencing. Bacterial community structure was different between channels and hybrids across all intestinal segments (<i>P</i> < 0.05) despite a lack of difference in community diversity. <i>Cetobacterium</i> spp. were found in higher abundances in the middle intestinal segment of hybrids compared with channels (<i>q</i> = 0.02) and found to have a trend of increasing abundance with increasingly distal segments in both channels and hybrids (<i>q</i> < 0.05). <i>Vibrio</i> spp., a low-abundance taxon, was similarly found in higher abundances in the anterior segment of hybrids. These results provide evidence of differences in the gut microbiomes of channels and hybrids and insight into the bacterial communities along the catfish intestinal tract. Additional research will be valuable in understanding why do differences between channel and hybrid catfish exist and how they may contribute to variation in gut microbiome-related production traits.<b>NEW & NOTEWORTHY</b> Hybrid and channel catfish are inhabited by gut bacterial communities of similar overall diversity but of significantly different structure and composition. <i>Cetobacterium</i> spp., a genus previously shown to confer benefits in other hosts, was found in higher abundances in the middle intestinal segment of hybrids and was found to have increasing abundance along the intestinal tract of both channels and hybrids.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"299-307"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524134","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":"Prolonged obesity alters males' adipose profile: implications for disease?","authors":"Jessica L Faulkner","doi":"10.1152/physiolgenomics.00191.2024","DOIUrl":"10.1152/physiolgenomics.00191.2024","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"254-255"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449761","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":"Developmental pyrethroid exposure disrupts molecular pathways for MAP kinase and circadian rhythms in mouse brain.","authors":"Jennifer H Nguyen, Melissa A Curtis, Ali S Imami, William G Ryan, Khaled Alganem, Kari L Neifer, Nilanjana Saferin, Charlotte N Nawor, Brian P Kistler, Gary W Miller, Rammohan Shukla, Robert E McCullumsmith, James P Burkett","doi":"10.1152/physiolgenomics.00033.2024","DOIUrl":"10.1152/physiolgenomics.00033.2024","url":null,"abstract":"<p><p>Neurodevelopmental disorders (NDDs) are a category of pervasive disorders of the developing nervous system with few or no recognized biomarkers. A significant portion of the risk for NDDs, including attention deficit hyperactivity disorder (ADHD), is contributed by the environment, and exposure to pyrethroid pesticides during pregnancy has been identified as a potential risk factor for NDD in the unborn child. We recently showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin in mice causes male-biased changes to ADHD- and NDD-relevant behaviors as well as the striatal dopamine system. Here, we used an integrated multiomics approach to determine the broadest possible set of biological changes in the mouse brain caused by developmental pyrethroid exposure (DPE). Using a litter-based, split-sample design, we exposed mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. We raised male offspring to adulthood, euthanized them, and pulverized and divided whole brain samples for split-sample transcriptomics, kinomics, and multiomics integration. Transcriptome analysis revealed alterations to multiple canonical clock genes, and kinome analysis revealed changes in the activity of multiple kinases involved in synaptic plasticity, including the mitogen-activated protein (MAP) kinase ERK. Multiomics integration revealed a dysregulated protein-protein interaction network containing primary clusters for MAP kinase cascades, regulation of apoptosis, and synaptic function. These results demonstrate that DPE causes a multimodal biophenotype in the brain relevant to ADHD and identifies new potential mechanisms of action.<b>NEW & NOTEWORTHY</b> Here, we provide the first evidence that low-dose developmental exposure to a pyrethroid pesticide, deltamethrin, results in molecular disruptions in the adult mouse brain in pathways regulating circadian rhythms and neuronal growth (MAP kinase). This same exposure causes a neurodevelopmental disorder (NDD)-relevant behavioral change in adult mice, making these findings relevant to the prevention of NDDs.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"240-253"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441601","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":"Alternative splicing of <i>CADM1</i> is associated with endothelial progenitor cell dysfunction in preeclampsia.","authors":"Ricarda Welz, Dhanya Ramachandran, Bianca Schröder-Heurich, Katja Richter, Robert Geffers, Constantin S von Kaisenberg, Thilo Dörk, Frauke von Versen-Höynck","doi":"10.1152/physiolgenomics.00006.2024","DOIUrl":"10.1152/physiolgenomics.00006.2024","url":null,"abstract":"<p><p>Preeclampsia is a pregnancy-specific hypertensive disorder and is associated with an increased postpartum risk of cardiovascular morbidity for both women and their offspring. Previous studies have indicated that cord blood endothelial colony-forming cells (ECFCs) are dysfunctional in preeclampsia. The specific mechanisms are not yet fully understood, but dysregulation of alternative splicing has been proposed as one of the pathogenic pathways. To identify specific targets of alternative splicing in fetal ECFCs, we performed transcriptome-wide differential splicing analyses between cord blood ECFCs from preeclamptic (<i>n</i> = 16) and normal pregnancies (<i>n</i> = 13). Selected splicing events were validated using fragment length analysis and Sanger sequencing. In silico transcriptome-wide differential splicing analysis identified a significantly increased abundance of the <i>CADM1</i> isoform ENST00000542447 in the preeclamptic cohort (<i>P</i> = 0.002), which was confirmed by wet-lab validation. The deleted exon 8 harbors glycosylation sites known to mediate cell-cell adhesion. To investigate the functional impact of alternative splice variants, we induced an in vitro splice switch using antisense morpholino treatment and then monitored cellular effects using migration and angiogenesis assays in ECFCs from six normal pregnancies. The <i>CADM1</i> exon 8 skipping converted the normal ECFCs to a preeclampsia-like state characterized by a decreased migration ability (<i>P</i>_ANOVA = 0.005) and decreased tubule length (<i>P</i>_ANOVA = 0.02). We propose aberrant splicing of <i>CADM1</i> and the resulting changes in the adherence properties of ECFCs as a potential contributor to cardiovascular sequelae in the offspring of preeclamptic pregnancies.<b>NEW & NOTEWORTHY</b> We investigated differential splicing between normal and preeclamptic pregnancies in endothelial colony-forming cells (ECFCs) from cord blood. Transcriptome-wide analysis identified exon 8 skipping of <i>CADM1</i> mRNA to be upregulated in ECFCs from women with preeclampsia. In vitro splice switching studies indicated that induction of this isoform decreases the cell migration and tubule formation abilities of fetal ECFCs. Our findings link a specific splice isoform of <i>CADM1</i> to preeclampsia, with potential implications for vascular health in the offspring.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"217-226"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391505","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":"Kidney cell response to acute cardiorenal and isolated kidney ischemia-reperfusion injury.","authors":"Kevin G Burfeind, Yoshio Funahashi, Xiao-Tong Su, Anne E Lackey, Matt W Hagen, Sienna Blanche, Jacqueline M Emathinger, Jessica F Hebert, Alicia A McDonough, Susan B Gurley, Jonathan W Nelson, Michael P Hutchens","doi":"10.1152/physiolgenomics.00161.2024","DOIUrl":"10.1152/physiolgenomics.00161.2024","url":null,"abstract":"<p><p>Acute cardiorenal syndrome (CRS) represents a critical intersection of cardiac and renal dysfunction with profound clinical implications. Despite its significance, the molecular underpinnings that mediate cellular responses within the kidney during CRS remain inadequately understood. We used single nucleus RNA sequencing (snRNAseq) to dissect the cellular transcriptomic landscape of the kidney following a translational model of CRS, cardiac arrest/cardiopulmonary resuscitation (CA/CPR) in comparison to ischemia-reperfusion injury (IRI). In each dataset, we found that proximal tubule (PT) cells of the kidney undergo significant gene expression changes, with decreased expression of genes critically important for cell identity and function, indicative of dedifferentiation. Based on this, we created a novel score to capture the dedifferentiation state of each kidney cell population and found that certain epithelial cell populations, such as the PT S1 and S2 segments, as well as the distal convoluted tubule, exhibited significant dedifferentiation response. Interestingly, the dedifferentiation response in the distal nephron differed in magnitude between IRI and CA/CPR. Gene set enrichment analysis (GSEA) of PT response to IRI and CA/CPR revealed similarities between the two models and key differences, including enrichment of immune system process genes. Transcriptional changes in both mouse models of acute kidney injury (AKI) highly correlated with a dataset of human biopsies from patients diagnosed with AKI. This comprehensive single-nucleus transcriptomic profiling provides valuable insights into the cellular mechanisms driving CRS.<b>NEW & NOTEWORTHY</b> Cardiac dysfunction is a common cause of acute kidney injury in a malady called acute cardiorenal syndrome. In a mouse model of acute cardiorenal syndrome called cardiac arrest/cardiopulmonary resuscitation, we characterized, for the first time, the kidney transcriptional landscape at the single-cell level. We developed a novel method for quantifying cell response to injury and found that cells adapted through dedifferentiation, the magnitude of which varied depending on cell type.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"266-278"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468052","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}