Genes最新文献

{"title":"Genomic Reanalysis of Neurodevelopmental Disorders With and Without Epilepsy: Diagnostic Yield and Mechanisms of Newly Established Diagnoses.","authors":"Da Hye Yoon, Chang Ahn Seol, Jung Woo Rhim, Ji Yoon Han","doi":"10.3390/genes17091078","DOIUrl":"10.3390/genes17091078","url":null,"abstract":"<p><strong>Background/objectives: </strong>Genomic reanalysis may provide additional molecular diagnoses in patients with neurodevelopmental disorders (NDDs) whose initial genetic testing was nondiagnostic. We evaluated the diagnostic yield and mechanisms of newly established diagnoses in NDDs with and without epilepsy.</p><p><strong>Methods: </strong>We retrospectively reviewed 175 patients with previously unresolved NDDs who underwent whole-exome sequencing between 2015 and 2024. Archived WES variant call format (VCF) files were reannotated using updated databases and variant prioritization criteria, followed by phenotype- and inheritance-informed clinical interpretation. Patients were classified as NDD without epilepsy (<i>n</i> = 133) or NDD with epilepsy (NDD+E; <i>n</i> = 42).</p><p><strong>Results: </strong>Five new molecular diagnoses were established, yielding an incremental diagnostic yield of 3% (5/175). The yield was numerically higher in the NDD+E group than in the NDD group (7% [3/42] vs. 2% [2/133]), although the difference was not statistically significant (<i>p</i> = 0.090). Newly established diagnoses involved <i>NPRL3</i>, <i>RYR1</i>, <i>SYNGAP1</i>, <i>CSNK2B</i>, and <i>SETD5</i> and arose through distinct mechanisms, including complementary CNV testing with retrospective sequencing review, phenotype- and inheritance-informed reinterpretation, recognition of insufficient initial sequencing coverage, and updated variant interpretation incorporating new evidence.</p><p><strong>Conclusions: </strong>Genomic re-evaluation provided additional diagnoses in a modest but clinically relevant proportion of previously unresolved pediatric NDD cases. Periodic, phenotype-informed reassessment of existing genomic data, together with complementary testing when indicated, may resolve diagnoses missed or uninterpretable at the initial evaluation.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHC-Related Shared Genetic Susceptibility Between Ulcerative Colitis and Gastric Cancer in East Asians.","authors":"Ji Eun Kim, Hyuk Lee, Young Eun Oh, Tae-Se Kim, Yang Won Min, Byung-Hoon Min, Jun Haeng Lee, Poong-Lyul Rhee","doi":"10.3390/genes17091077","DOIUrl":"10.3390/genes17091077","url":null,"abstract":"<p><strong>Background/objectives: </strong>Observational studies in East Asia have not shown increased gastric cancer risk in ulcerative colitis, whereas a previous genetic analysis reported a positive association. Because both diseases have major histocompatibility complex (MHC) signals, we assessed whether the association was most apparent in MHC variants under ancestry-matched instrument selection.</p><p><strong>Methods: </strong>We performed a two-stage, two-sample Mendelian randomization study of 12 East Asian datasets (11 immune-related phenotypes) and a gastric cancer genome-wide association study (7921 cases; 159,201 controls), with instruments selected against the 1000 Genomes East Asian panel. For ulcerative colitis, we compared all, MHC, and non-MHC variants, evaluated signal overlap at <i>HLA-DQA1/DQB1</i>, and assessed cross-disease specificity.</p><p><strong>Results: </strong>Ulcerative colitis was the only phenotype associated with gastric cancer after false-discovery-rate correction (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.09-1.24; q = 1.37 × 10^-4). The MHC estimate was similar (OR 1.18, 95% CI 1.11-1.26), whereas the non-MHC estimate was close to 1 but rested on only two variants and remained imprecise (OR 1.00, 95% CI 0.86-1.17). The traits showed overlapping signals at <i>HLA-DQA1/DQB1</i>, and the MHC variants were associated with several other immune diseases.</p><p><strong>Conclusions: </strong>The positive association was most apparent in MHC variants that were not specific to ulcerative colitis. The association therefore appears to be largely carried by pleiotropic MHC variants, although these data cannot establish the pathway that explains it.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning-Guided Identification and In Vivo Validation of Compact Cis-Regulatory Elements for the Zebrafish Habenula.","authors":"Zeran Li, Shanshan Liu, Quan Zhang, Cuizhen Zhang, Gang Peng","doi":"10.3390/genes17091079","DOIUrl":"10.3390/genes17091079","url":null,"abstract":"<p><strong>Background/objectives: </strong>Precise genetic access to the zebrafish habenula remains limited by a scarcity of compact, sequence-defined cis-regulatory elements (CREs). Here, we integrated developmental expression mapping, deep-learning predictions on long-range sequences, and in vivo reporter assays to identify compact regulatory sequences driving habenular expression.</p><p><strong>Methods: </strong>Using a transgenic zebrafish line enriched for habenular reporter expression, we isolated GFP-positive cells from larval brains and profiled their transcriptomes via microarray. A subset of candidate genes enriched in this dataset was validated using whole-mount in situ hybridization across two developmental stages. This analysis identified genes with highly reproducible habenular expression, leading to the selection of the <i>gng8</i> and <i>ano2</i> loci for subsequent CRE characterization. We developed ZEN-former (Zebrafish EN-former), an Enformer-based sequence-to-function model trained on neuronal subclass chromatin accessibility profiles from the adult mouse brain.</p><p><strong>Results: </strong>The model demonstrated strong correlation between predicted and experimentally measured signals across held-out genomic regions. To prioritize regulatory candidates, we integrated ZEN-former predictions with available zebrafish ATAC-seq data, RepeatMasker annotations, and gene models, identifying two ~600 bp intervals at each gene locus. These selected intervals were combined to generate ~1.2 kb reporter constructs for <i>gng8</i> and <i>ano2</i> loci, which were then evaluated using Tol2 transposon mediated transgenesis assays in zebrafish. In transiently injected larvae, both constructs successfully drove reporter expression in the habenular region. Furthermore, the resulting stable transgenic lines displayed highly specific and reproducible habenular expression. Quantitative confocal analysis showed mean habenular labeling completeness values of 84.5% and 96.2% for the <i>gng8</i>- and <i>ano2</i>-derived lines, respectively.</p><p><strong>Conclusions: </strong>Together, these findings provide a proof of concept that sequence features learned from mammalian chromatin accessibility datasets can effectively guide the prioritization of functional regulatory elements across species in zebrafish. The compact regulatory constructs and stable transgenic lines generated here offer robust genetic tools for investigating habenular circuitry.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel <i>ZmLG1</i> Allele as a Genetic Resource for Breeding Compact Plant Architecture in Maize.","authors":"Yue Feng, Haimo Zhu, Shiyi Zhong, Lijing Wang, Yan Zhao, Wei Xu, Qingzhi Liu, Shengkun Liu, Baoshen Liu, Yongzhong Zhang","doi":"10.3390/genes17091075","DOIUrl":"10.3390/genes17091075","url":null,"abstract":"<p><strong>Background: </strong>Leaf angle is a key determinant of plant architecture and yield under high-density planting. Loss of the ligule reduces leaf angle, offering a strategy for breeding compact maize. This study aims to identify the genetic basis of the liguleless mutant <i>jd30</i> and develop a functional marker for breeding.</p><p><strong>Methods: </strong>The <i>jd30</i> mutant was phenotypically characterized and compared with the wild type (WT). Genetic analysis was performed using F₂ populations. Map-based cloning was conducted with simple sequence repeat (SSR) and insertion/deletion (InDel) markers. Candidate genes were annotated and sequenced. Allelism tests were performed by crossing <i>jd30</i> with other <i>lg1</i> mutants. A Cleaved Amplified Polymorphic Sequence (CAPS) marker was developed based on the causal mutation.</p><p><strong>Results: </strong>The <i>jd30</i> mutant showed complete ligule loss from the V2 stage onward and had a significantly smaller leaf angle than the wild type. The phenotype is controlled by a single recessive nuclear gene, mapped to a 123-kb interval on chromosome 2 containing four candidate genes. A single-base cytosine (C) deletion at nucleotide 522 of <i>ZmLG1</i> caused a frameshift and premature stop codon. Two other <i>lg1</i> mutants, <i>20292</i> and <i>29163</i>, carried distinct mutations-a C insertion and multiple base substitutions, respectively. Allelism tests confirmed <i>jd30</i> as a novel allele of <i>ZmLG1</i>. A co-dominant CAPS marker, <i>M5</i>, was developed to distinguish wild-type and mutant alleles.</p><p><strong>Conclusions: </strong>This study identifies a novel loss-of-function allele of <i>ZmLG1</i>, designated <i>ZmLG1-1</i>, and the <i>M5</i> marker, providing valuable genetic resources for modifying leaf architecture and improving maize plant compactness.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Coding RNA Biomarkers in Male Infertility: From Discovery to Clinical Actionability-A Narrative Review.","authors":"Aris Kaltsas, Eleftheria Markou, Athanasios Zachariou, Fotios Dimitriadis, Nikolaos Sofikitis","doi":"10.3390/genes17091074","DOIUrl":"10.3390/genes17091074","url":null,"abstract":"<p><p>Non-coding RNAs (ncRNAs) are biologically plausible biomarkers in male infertility, but no assay is ready for routine use. This narrative review organizes human evidence by intended clinical decision and defines clinical actionability as a test's ability to inform a specified decision through analytical reliability, clinical validity, incremental value, decision-level benefit, and feasible implementation. Evidence is most developed for obstructive versus non-obstructive azoospermia (NOA) classification and sperm-retrieval prognosis. Most reports, however, use selected case-control samples, single-center development cohorts, or same-program evaluations. Mixed biospecimens, incompletely specified RNA isoforms and normalization, uncertain cohort independence, imperfect diagnostic references, and protocol-dependent retrieval outcomes limit transportability. No independent geographic validation of a locked ncRNA assay or prospective evaluation of ncRNA-guided management was identified within the retrieved sources. Current guidelines do not recommend routine ncRNA testing. Progress requires prespecified intended uses, locked assays, representative multicenter validation, same-patient comparison with contemporary care, calibrated risk estimates, decision-curve analysis, and patient-important, couple-centered outcomes.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interference of Small Sequence Variants with MLPA in <i>CLCN1</i>: Implications for Congenital Myotonia Diagnosis.","authors":"Maria Busacca, Eleonora Canioni, Raffaella Brugnoni","doi":"10.3390/genes17091073","DOIUrl":"10.3390/genes17091073","url":null,"abstract":"<p><strong>Background/objectives: </strong>Congenital myotonia (CM) is an inherited neuromuscular disorder caused by mutations in the Chloride Voltage-Gated Channel 1 (<i>CLCN1</i>) gene, encoding the Chloride Channel 1 (CIC-1) in skeletal muscle. These mutations can be inherited in either an autosomal dominant (Thomsen's disease) or recessive pattern (Becker's disease). Within the diagnostic workflow for this pathology, gene sequencing represents one of the main analytical approaches, while Multiplex Ligation-dependent Probe Amplification (MLPA) is used as a complementary method, particularly in patients with autosomal recessive inheritance, to detect deletions or duplications involving one or more exons of the <i>CLCN1</i>. This study aims to highlight a specific limitation of MLPA in <i>CLCN1</i> analysis.</p><p><strong>Methods: </strong>Patients carrying pathogenic <i>CLCN1</i> variants, previously identified by sequencing, subsequently underwent MLPA analysis to investigate the presence of a second pathogenic allele.</p><p><strong>Results: </strong>In the analysed patients, MLPA identified apparent exon deletions involving the same exons in which the previously identified variants were present. However, no actual variation in copy number was observed at the exon level. This discrepancy is linked to the efficiency of probe hybridization and ligation to target sequences. Small sequence variations can interfere with probe binding, preventing their correct ligation and resulting in a signal pattern consistent with apparent exon loss, thereby generating false positives.</p><p><strong>Conclusions: </strong>Our findings highlight the importance of integrating sequencing and MLPA data in <i>CLCN1</i> analysis. Awareness of variant-induced MLPA artefacts is essential to avoid misinterpretation of apparent exon deletions and to ensure an accurate molecular diagnosis of CM.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Calcipotriol-Responsive ZF10-ΔVDR Switch for Mammalian Transgene Regulation with Topical Induction In Vivo.","authors":"Hong Su, Shiting Li, Guanyang Chen, Peng Bai","doi":"10.3390/genes17091072","DOIUrl":"10.3390/genes17091072","url":null,"abstract":"<p><strong>Background: </strong>Small-molecule-regulated gene switches are important tools for programmable mammalian cell engineering, and compact switches responsive to clinically familiar ligands that can be administered locally are particularly attractive for externally regulated transgene expression.</p><p><strong>Methods: </strong>Here, we developed ZF10-ΔVDR, a compact zinc-finger-VDR transcriptional switch, by fusing an orthogonal human-derived zinc-finger array, ZF10, to the hinge and ligand-binding domain of the vitamin D receptor. The resulting switch enabled transgene regulation by calcipotriol, a clinically used topical vitamin D analog and VDR agonist.</p><p><strong>Results: </strong>ZF10-ΔVDR maintained low basal activity, showed limited activation by the tested vitamin D species at physiologically relevant reference concentrations, and was robustly activated by calcipotriol. The system functioned across multiple human cell types. In vivo, topical calcipotriol increased serum reporter output in mice bearing subcutaneous microencapsulated-cell implants, whereas oral vitamin D3 did not measurably activate this system under the tested conditions. In a separate HaCaT implantation model, topical calcipotriol increased bioluminescence at wound-adjacent implantation sites. ZF10-ΔVDR also supported reversible ON/OFF cycling under the tested conditions and inducible secreted protein output in vitro.</p><p><strong>Conclusions: </strong>These findings establish ZF10-ΔVDR as a calcipotriol-responsive switch with limited activation by endogenous vitamin D species, activity across multiple mammalian cell types, reversible regulation under the tested conditions, and compatibility with topical induction in vivo.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Functional Characteristics of <i>NR5A1</i> Gene Variant in Patients with 46,XY Disorders of Sex Development.","authors":"Lin He, Liangzhe Li, Yuxiao Li, Yujun Sun, Zhi Zheng, Chunfang Chu, Shuya Chen, Lin Li","doi":"10.3390/genes17091070","DOIUrl":"10.3390/genes17091070","url":null,"abstract":"<p><strong>Background/objectives: </strong>Individuals with 46,XY disorders of sexual development (DSD) present with incomplete genital masculinization, aberrant gonadal development, and occasional retention of Müllerian duct remnants. Genetic factors play a substantial role in DSD pathogenesis, and whole-exome sequencing has expanded the catalog of candidate variants in recent years. However, the underlying molecular pathways remain incompletely characterized, and the functional relevance of most isolated genetic findings has not been systematically determined. This study aimed to identify and functionally characterize novel <i>NR5A1</i> variants in DSD.</p><p><strong>Methods: </strong>A heterozygous missense variant <i>NR5A1</i> c.88T>A (p.Cys30Ser) was identified in two patients with DSD, and initial functional characterization of the variant was performed via immunofluorescence analysis, Western Blotting, RNA sequencing, and quantitative real-time PCR analysis.</p><p><strong>Results: </strong>Wildtype NR5A1 protein localized predominantly to the nucleus, whereas the p.Cys30Ser mutant exhibited dual nuclear and cytoplasmic distribution. Compared with the wildtype, the p.Cys30Ser variant altered the expression of 642 genes, with differentially expressed genes primarily enriched in the neuroactive ligand-receptor interaction pathway. The variant impaired the transactivation of canonical <i>NR5A1</i> downstream targets, resulting in the marked downregulation of 560 genes including key regulators such as <i>KISS1R</i>, <i>CYP11A1</i>, <i>STAR</i>, <i>GABRP</i>, and <i>GRAMD1D</i>.</p><p><strong>Conclusions: </strong>This study is the first to identify and functionally characterize the <i>NR5A1</i> p.Cys30Ser variant in the context of DSD. Our findings broaden the mutational spectrum of <i>NR5A1</i>-related DSD and provide new insights into the molecular genetic basis of sexual development disorders.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Medicine in Pediatric Nephrology: From Shared Clinical Phenotypes to Genotype-Guided Diagnosis and Management.","authors":"John Dotis, Nikoleta Printza","doi":"10.3390/genes17091069","DOIUrl":"10.3390/genes17091069","url":null,"abstract":"<p><p>Pediatric nephrology is shifting from broad phenotype-based labels toward molecularly defined, genotype-guided diagnosis and management. Childhood kidney disorders are enriched for monogenic causes, yet persistent microscopic hematuria, bilateral kidney cysts, steroid-resistant nephrotic syndrome, and thrombotic microangiopathy may represent shared endpoints of biologically distinct mechanisms. Using these four scenarios, this narrative review illustrates how structured phenotyping, pedigree analysis, biochemical evaluation, and appropriately selected genomic testing can establish etiology, revise diagnoses, and guide clinical decision-making. Molecular diagnosis may support early nephroprotection, prevent ineffective immunosuppression, reveal tumor or extrarenal risks, enable mechanism-based therapy, and optimize transplantation planning. It also enables cascade testing, reproductive counseling, presymptomatic evaluation of relatives, and safer assessment of living-related donors. Genomic findings, however, require clinical context. Variants must be evaluated against gene-disease validity, inheritance, segregation, molecular mechanism, and phenotype, while variants of uncertain significance should not independently determine treatment or donor eligibility. Negative or inconclusive findings should prompt phenotypic reassessment, evaluation of analytical limitations, targeted studies, and periodic genomic reanalysis. Emerging genome and long-read sequencing, multiomics, artificial intelligence, and RNA-based therapeutics may further expand precision care, but rigorous interpretation, equitable access, appropriate counseling, and multidisciplinary collaboration remain essential. Precision nephrology derives value not from identifying variants alone, but from converting molecular etiology into safer, anticipatory, and individualized care.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Single-Nucleus Transcriptomic Analysis of the Intact Left Ventricle in <i>Acomys cahirinus</i> and <i>Mus musculus</i>.","authors":"Nikita Filatov, Kirill Kokorichev, Dmitry Tychinin, Taisiya Voronina, Elena Shagimardanova, Konstantin Dergilev, Pavel Makarevich, Andrey Kiyasov, Vsevolod Tkachuk, Mary Woroncow, Yelena Parfyonova, Airat Bilyalov, Oleg Gusev","doi":"10.3390/genes17091071","DOIUrl":"10.3390/genes17091071","url":null,"abstract":"<p><strong>Background/objectives: </strong><i>Acomys cahirinus</i> exhibits more favorable cardiac remodeling after ischemic injury than <i>Mus musculus</i>, yet the molecular organization of the intact myocardium remains poorly characterized. This study aimed to identify baseline interspecies differences in the adult left ventricle, with particular emphasis on ventricular cardiomyocyte transcriptional states.</p><p><strong>Methods: </strong>Intact left ventricles from adult male <i>A. cahirinus</i> and <i>M. musculus</i> were analyzed by single-nucleus RNA sequencing using three biological samples per species. Cross-species integration was followed by cell type annotation, pseudobulk differential expression analysis, Augur-based assessment of interspecies separability, coexpression module analysis, and focused reintegration analysis of ventricular cardiomyocytes. Cardiomyocyte profiles were further compared with published embryonic and early postnatal <i>M. musculus</i> heart datasets.</p><p><strong>Results: </strong>Both species contained comparable major myocardial cell populations, whereas marked interspecies transcriptional differences persisted within individual cell types. Ventricular cardiomyocytes exhibited the largest number of differentially expressed genes and were classified into three transcriptional states: contractile, matrix-associated, and alternative. Adult <i>A. cahirinus</i> cardiomyocytes retained a mature cardiomyocyte phenotype but showed greater enrichment of developmental, morphogenetic, and Hippo-associated gene programs than adult <i>M. musculus</i> cardiomyocytes. Their transcriptional profile did not correspond to embryonic or early postnatal mouse states. The integrated atlas further identified interspecies differences in fibroblast-associated and extracellular matrix-related programs.</p><p><strong>Conclusions: </strong>The intact myocardium of <i>A. cahirinus</i> exhibits cell type-specific transcriptional differences relative to <i>M. musculus</i>. Ventricular cardiomyocytes display a distinct mature transcriptional configuration rather than a direct immature state, which may contribute to the favorable response of <i>A. cahirinus</i> to myocardial injury.</p>","PeriodicalId":12688,"journal":{"name":"Genes","volume":"17 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13606643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}