Functional & Integrative Genomics最新文献

{"title":"Identification of rice DUF1719 gene family and analysis of alkaline tolerance function of OsDUF1719.8","authors":"Jing Su,&nbsp;Yangmengfei She,&nbsp;Tinglu Liao,&nbsp;Donghao Xiao,&nbsp;Yanqi Wang,&nbsp;Chengke Luo","doi":"10.1007/s10142-026-02028-2","DOIUrl":"10.1007/s10142-026-02028-2","url":null,"abstract":"<div><p>Alkaline stress severely constrains the physiological metabolism and growth and development of rice through high pH and ionic toxicity. Domains of unknown function (DUF) play significant roles in plant stress responses. However, the function of the DUF1719 family (PF08224) in rice has not been reported and further research is needed. This study systematically identified the OsDUF1719 gene family in rice and investigated the function of <i>OsDUF1719.8</i> under alkaline stress. The results demonstrate that the rice DUF1719 family comprises 13 protein members, all containing the PF08224 domain. It is predicted that this domain may play a role in ATPase activation. Evolutionary analysis divided DUF1719 proteins from eight grass species into six subgroups, with highly conserved gene structures, motifs, and tertiary architectures within each subgroup. Promoter analysis indicated enrichment of stress- and hormone-responsive elements, implying broad involvement in stress regulation. Expression analysis revealed that several genes, including <i>OsDUF1719.5</i> and <i>OsDUF1719.8</i>, were upregulated under multiple abiotic stresses. Notably, <i>OsDUF1719.8</i> was strongly induced during early alkaline stress. Consequently, we further analyzed the function of <i>OsDUF1719.8</i> in the rice alkaline stress response. The results demonstrate that overexpression of <i>OsDUF1719.8</i> enhanced rice alkaline tolerance, whereas knockout mutants exhibited stress sensitivity. <i>OsDUF1719.8</i> enhances rice tolerance to alkaline stress by coordinately regulating reactive oxygen species metabolism, promoting the accumulation of osmotic adjustment compounds, and modulating ion homeostasis. This study provides the first systematic identification of the DUF1719 family and elucidates the function of <i>OsDUF1719.8</i> in positively regulating rice alkaline tolerance, offering a novel gene for alkali-tolerant molecular breeding of rice.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890608","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":"Oral and gut microbiota profiles in patients with locally advanced rectal cancer with varying responses to neoadjuvant chemoradiotherapy","authors":"Yajing Wen,&nbsp;Ziqian Luo,&nbsp;Zhemin Li,&nbsp;Kexin Li,&nbsp;Jiaying Li,&nbsp;Shengqi Yin,&nbsp;Yishu Zou,&nbsp;Huilian Zhang,&nbsp;Yuqin Zhang,&nbsp;Keli Chen,&nbsp;Yaowei Zhang,&nbsp;Shupeng Liu,&nbsp;Zhenhui Chen,&nbsp;Lu Yu,&nbsp;Yi Ding","doi":"10.1007/s10142-026-02025-5","DOIUrl":"10.1007/s10142-026-02025-5","url":null,"abstract":"<div><p>Recent research has focused on gut bacteria in colorectal cancer, but the influence of other microbiota, including oral and nonbacterial gut microbiota, on treatment efficacy remains insufficiently explored. This study aimed to investigate their relationship with the efficacy of neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Saliva and fecal samples were collected from patients with LARC before treatment. Shotgun metagenomic sequencing was used to profile bacterial, archaeal, eukaryotic, and viral taxonomic groups and to examine oral and gut microbial functions. An artificial intelligence-based prediction model was developed by integrating oral and gut microbiome data with clinical information. Statistical analyses compared diversity and response-associated microbial features between responders and non-responders to nCRT. Response-associated differences were observed in bacterial and nonbacterial taxonomic profiles and in oral and gut microbial functional profiles. In the internal test subset, the integrated analysis yielded an observed AUC of 0.917. Given the small cohort and the exploratory comparison of candidate classifiers, this estimate requires confirmation in larger, independent cohorts. Baseline oral and gut microbiome profiles were associated with response to nCRT. Integrating microbiome and clinical features showed potential for response prediction, but the model remains exploratory and requires validation in larger, independent cohorts before clinical application. Retrospectively registered on 01/08/2026, NCT07346729.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885974","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":"Integrating genomics, multi-omics, CRISPR and speed breeding for stress-resilient vegetable legume improvement","authors":"Sandeep Indurthi,&nbsp;Gurpreet Kaur,&nbsp;Rituraj Dutta,&nbsp;Saatu Madhu,&nbsp;Bhaskar Chodasani,&nbsp;Amul Yadav,&nbsp;Manpreet Singh,&nbsp;Tarun Kumar Meena,&nbsp;Gurjeet Singh","doi":"10.1007/s10142-026-02037-1","DOIUrl":"10.1007/s10142-026-02037-1","url":null,"abstract":"<div><p>Vegetable legumes are nutritionally and ecologically important crops. However, their genetic improvement has not kept pace with the increasing challenges posed by climate change due to the polygenic nature of stress tolerance, narrow genetic diversity, and the persistent gap between molecular discoveries and field-level cultivar development. Although recent reviews have examined individual genomic tools or specific stress responses, a comprehensive synthesis integrating genomics-assisted breeding, multi-omics technologies, genome editing, and speed breeding within a unified crop improvement framework has been lacking. This review addresses that gap by critically evaluating how these complementary approaches can accelerate the development of stress-resilient vegetable legumes, including pea, common bean, cowpea, faba bean, cluster bean, yard-long bean, and hyacinth bean. This review synthesizes advances in QTL mapping, genome-wide association studies, transcriptomics, metabolomics, and CRISPR-based functional genomics that have identified key regulators and pathways underlying resistance to major biotic and abiotic stresses. Rather than considering these technologies independently, the review emphasizes their convergence into a systems-level breeding framework integrating genomic discovery, functional validation, predictive breeding, and accelerated generation advancement to improve breeding efficiency. Speed breeding, enabling up to seven to eight generations annually under optimized controlled-environment experimental conditions in cowpea, is discussed as a complementary strategy with genomic selection and genome editing. The review further identifies major translational bottlenecks, including transformation recalcitrance, limited genomic resources for underutilized vegetable legumes, inadequate multi-environment validation, and fragmented omics integration, and presents an integrated systems-breeding framework to bridge the gap between gene discovery and cultivar development.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885943","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":"CRISPR–cas systems in pharmacology: functional pharmacogenomics, drug screening, resistance, and therapeutic translation","authors":"Muhammad Saeed Akhtar,&nbsp;Adnan Amin","doi":"10.1007/s10142-026-02026-4","DOIUrl":"10.1007/s10142-026-02026-4","url":null,"abstract":"<div><p>CRISPR-Cas9 gene-editing technology has advanced pharmacological research by enabling targeted genetic modification for disease modeling, therapeutic development, and precision medicine. This review discusses the applications of CRISPR-Cas9 in drug discovery, personalized therapy, cancer drug resistance research, genetic disorders, and antimicrobial resistance. By editing disease-associated genes, CRISPR-Cas9 supports the development of patient-specific therapeutic strategies and more accurate preclinical models. In cancer, CRISPR-Cas9 is used to investigate the target genes involved in treatment resistance, while in genetic disorders, it offers potential mutation-correcting approaches, with the most robust clinical evidence currently seen in selected hemoglobinopathies. CRISPR-based strategies also hold promise for restoring antibiotic susceptibility by targeting genes that confer antibiotic resistance. Despite these advances, clinical translation remains limited by off-target effects, delivery challenges, immune responses, long-term safety concerns, and ethical and regulatory issues. Continued improvements in editing precision, delivery systems, and governance frameworks are essential for responsible clinical integration. Overall, CRISPR-Cas9 represents a vital platform for future pharmacological innovation, but its broad clinical use may require further validation of safety, efficacy, durability, and accessibility.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872455","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":"Association of PCSK9 and CCL22 gene polymorphisms with myocardial infarction in a South Indian population","authors":"Praveen Kumar Chandra Sekar,&nbsp;Ashok Govindaraj,&nbsp;Ramakrishnan Veerabathiran","doi":"10.1007/s10142-026-02031-7","DOIUrl":"10.1007/s10142-026-02031-7","url":null,"abstract":"<div><p>Myocardial infarction (MI) remains a major global cause of morbidity and mortality, with a particularly high burden among individuals with type 2 diabetes mellitus (T2DM). Host genetic factors play a significant role in modulating individual susceptibility to MI by influencing lipid metabolism and immune-mediated inflammatory pathways. The proprotein convertase subtilisin/kexin type 9 (<i>PCSK9</i>) gene is a key regulator of cholesterol homeostasis, while C–C motif chemokine ligand 22 (<i>CCL22</i>) is involved in immune cell recruitment and vascular inflammation. In this study, we investigated the association of <i>PCSK9 rs505151</i> and <i>rs11591147</i> and <i>CCL22 rs4359426</i> polymorphisms with MI risk in a South Indian population. This case–control study included 400 participants categorized into controls (<i>n</i> = 100), MI (<i>n</i> = 100), T2DM (<i>n</i> = 100), and MI with T2DM (<i>n</i> = 100). Significant differences in clinical and biochemical parameters, including lipid indices and cardiometabolic risk markers, were observed between groups (<i>p</i> &lt; 0.05). Genetic analysis revealed a significant association between the <i>PCSK9 rs505151</i> variant and MI susceptibility across allelic and genotypic distributions, with significant effects under dominant and recessive inheritance models. Multivariable logistic regression confirmed that the <i>rs505151</i> risk genotype was independently associated with MI after adjustment for age, sex, body mass index, and smoking status. In contrast, <i>PCSK9 rs11591147</i> was rare and showed no significant association. The <i>CCL22 rs4359426</i> polymorphism showed limited evidence of association with MI, with a significant effect observed only under the dominant inheritance model. Furthermore, combined analysis using a genetic risk score suggested that cumulative genetic burden involving <i>PCSK9</i> and <i>CCL22</i> variants was associated with an increased risk of MI. Overall, our findings suggest that genetic variation in lipid-regulatory and immune-related pathways may contribute to MI susceptibility in South Indians. Further studies are warranted to validate these associations and clarify their biological and clinical relevance.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872482","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":"Shared genetic architecture and cellular convergence between female reproductive disorders and pulmonary function: a genome-wide cross-trait analysis","authors":"Enting Ji,&nbsp;Ze Wang,&nbsp;Shuting Ning,&nbsp;Yao Lu,&nbsp;Hongxia Ma","doi":"10.1007/s10142-026-02029-1","DOIUrl":"10.1007/s10142-026-02029-1","url":null,"abstract":"<div><p>Female reproductive disorders (FRDs), including polycystic ovary syndrome, endometriosis, uterine leiomyomata, and infertility, have been epidemiologically associated with impaired pulmonary function. However, it remains unclear whether this cross-organ link reflects shared genetic etiology and, if so, which cellular mechanisms mediate it. We performed a systematic genome-wide cross-trait analysis of three FRDs and lung function traits (FEV₁, FVC, FEV₁/FVC) using GWAS summary statistics from individuals of European ancestry, integrating genetic correlation, bidirectional causal inference, pleiotropy mapping, and single-cell enrichment analyses. We identified significant negative genetic correlations between FRDs and lung volume traits, most prominently for FVC (rg range: − 0.077 to − 0.178). Bidirectional causal analyses indicated that FRDs have a detrimental effect on lung volume, with higher FRD genetic liability associated with reduced lung volume. Cross-trait meta-analysis identified 17 pleiotropic variants across 11 loci, with the 19q13.2 (<i>LTBP4</i>) and 12q13.13 (<i>HOXC6</i>/<i>HOXC9</i>) loci showing strong evidence of shared causal variants. Critically, single-cell analyses revealed that shared genetic risk converged on mesenchymal lineages across organs, specifically alveolar adventitial fibroblasts in the lung and stromal/smooth muscle cells in the endometrium. Transcriptome-wide analyses further nominated the estrogen-responsive gene <i>RERG</i> as a convergent gene linking these conditions with lung function. Our study revealed a shared genetic architecture between female reproductive disorders and lung function traits, providing a basis for further mechanistic investigations and potential clinical evaluation. Furthermore, our findings suggest that shared fibroproliferative and hormone-responsive pathways may offer insights into the biological mechanisms underlying these conditions.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872452","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":"Genome-wide identification and evolution of the RCP gene family in soybean uncovers stress-responsive candidates","authors":"Xiaoli Guan,&nbsp;Run Yuan,&nbsp;Ao Shen,&nbsp;Yanhong Wang,&nbsp;Yuanmeng Yu,&nbsp;Liying Zou,&nbsp;Yuming Yang,&nbsp;Jinyu Zhang,&nbsp;Zhongwen Huang,&nbsp;Li Wang","doi":"10.1007/s10142-026-01853-9","DOIUrl":"10.1007/s10142-026-01853-9","url":null,"abstract":"<div><p>Abiotic stress has a significant impact on soybean growth, development, and yield. Proteins containing the Regulator of Chromosome Condensation 1 (RCC1) domain, known as RCPs, play important roles in plant stress responses. However, systematic analysis of the <i>RCP</i> gene family in soybean remains limited. In this study, a total of 52 <i>GmRCP</i> genes were identified in the soybean genome and classified into nine phylogenetic clades. Members within the same clade exhibited similar domain architectures. Collinearity analysis suggested that segmental duplication served as the major driver for the expansion of this gene family, and most duplicated gene pairs underwent purifying selection. Analysis of gene structure and conserved motifs revealed high conservation within clades but divergence among them, indicating potential functional diversification of <i>GmRCPs</i>. Furthermore, promoter analysis identified abundant cis-acting elements associated with hormone signaling and stress responses. Expression profiling demonstrated that most <i>GmRCP</i> genes were expressed across various soybean tissues, and several members were responsive to salt, drought, and low-phosphorus stresses. Notably, <i>GmRCP31</i>, <i>GmRCP43</i>, and <i>GmRCP46</i> were induced under multiple stresses, suggesting their potential roles in stress adaptation. These findings provide important insights into the functional diversity and evolutionary history of <i>GmRCP</i> genes and establish a foundation for further investigation of their roles in soybean development and stress resistance.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872490","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":"Integration of artificial intelligence and multi-omics for precision medicine","authors":"Hany E. Marei,&nbsp;Carlo Cenciarelli,&nbsp;David Vagni","doi":"10.1007/s10142-026-02024-6","DOIUrl":"10.1007/s10142-026-02024-6","url":null,"abstract":"<div><p>Precision medicine requires computational methods that can integrate genomic, transcriptomic, proteomic, metabolomic, epigenomic, single-cell and spatial measurements into decisions about individual patients, and artificial intelligence has become the enabling technology for doing so. This review argues that the binding constraint is no longer modelling capability but validation, calibration and governance. We compare seventeen multi-omics integration algorithms on the sample sizes they actually require and on whether independent groups have reproduced them; we set classical machine learning against deep learning by omics task and sample-size regime, and find that penalised regression and tree ensembles remain competitive wherever the number of samples is small relative to the number of features. We then examine seven documented failures of deployed clinical artificial intelligence, trace each to its root cause, and derive an eighteen-item appraisal checklist adapting existing reporting and risk-of-bias instruments to the failure modes of molecular data. Calibration, uncertainty quantification, batch effects and information leakage are treated as first-class problems rather than caveats. To show what leakage costs, we analysed 696 breast tumours with matched transcriptomic and copy-number profiles under randomly permuted labels, where the only honest result is chance. A pipeline that selects features before splitting the data reports an area under the receiver operating characteristic curve of 0.95 in cohorts of forty and 0.65 on the full cohort; the corresponding leak-free pipeline returns 0.50 at every size. What limits clinical adoption is the evidence a model can be held to, not the sophistication of the model.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863197","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":"An integrative multi-project transcriptomic and structural prediction framework identifies candidate cold-responsive transcription factors in Medicago sativa","authors":"Huixin Jiang,&nbsp;Meng Wang,&nbsp;Xiaoyue Zhu,&nbsp;Ruixin Zhang,&nbsp;Lina Dong,&nbsp;Changhong Guo,&nbsp;Yongjun Shu","doi":"10.1007/s10142-026-02027-3","DOIUrl":"10.1007/s10142-026-02027-3","url":null,"abstract":"<div><p>Cold stress limits alfalfa (<i>Medicago sativa</i>) growth and persistence, but public transcriptomic datasets differ widely in genotype, tissue, treatment duration, and experimental design. We integrated RNA-seq data from ten independent BioProjects using a common processing workflow while retaining project-specific structures. A recurrent contrast-level DEG-derived pool of 4,354 genes was ranked by random forest using expression profiles from 240 samples. The original model showed strong internal discrimination (OOB ROC–AUC = 0.937), whereas fully nested leave-one-BioProject-out validation yielded an accuracy of 0.729, balanced accuracy of 0.676, and ROC–AUC of 0.727. PlantTFDB annotation identified MsG0680033896.01, MsG0680033848.01, and MsG0480021906.01 as the three highest-ranked transcription factors. The first two candidates showed greater stability in project-held-out and alternative machine-learning analyses. In project-aware multilevel meta-analysis, neither the primary 50-contrast analysis nor the 54-contrast sensitivity analysis identified genome-wide significant transcripts after Benjamini–Hochberg correction. However, MsG0680033896.01 and MsG0680033848.01 showed predominantly positive effects, positive pooled estimates, and confidence intervals excluding zero in both analyses, whereas MsG0480021906.01 showed weaker directional consistency. Co-expression, promoter prediction, chromosomal localization, and AlphaFold3 modeling provided additional computational context, including localization of the two leading candidates within a Chr6 CBF/DREB1-like-enriched region. These results prioritize MsG0680033896.01 and MsG0680033848.01 as high-confidence computational candidates and retain MsG0480021906.01 as an additional project-sensitive candidate for future functional testing.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863262","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":"Decoding the senescent endothelial landscape in ischemic stroke through single-cell and bulk RNA sequencing","authors":"Lingyue Zhang,&nbsp;Yanyi Peng,&nbsp;Bo Xiao,&nbsp;Mengqi Zhang","doi":"10.1007/s10142-026-02018-4","DOIUrl":"10.1007/s10142-026-02018-4","url":null,"abstract":"<div><p>Ischemic stroke is a major cause of disability and mortality worldwide, but its underlying pathogenic mechanisms remain elusive. Although cellular senescence has been implicated in a wide range of age-related diseases, its specific contribution through endothelial cells to ischemic stroke pathogenesis remains unclear. To address this gap, the present study adopted an integrative strategy, combining single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq), to systematically characterize the senescent endothelial landscape in ischemic stroke. We identified a distinct senescence-associated gene signature in endothelial cells and highlighted four key genes—— Arhgap31, Tm4sf1, Itm2a, and Vwa1——that were closely associated with ischemic stroke pathogenesis. These genes showed differential expression and apparent discriminatory potential in the discovery bulk RNA-seq dataset, and external validation using independent scRNA-seq and cerebral microvessel bulk RNA-seq datasets provided additional support for the signature, particularly for Arhgap31, Tm4sf1, and Vwa1. Pathway enrichment and transcription factor analyses suggested potential pathways and upstream regulators associated with these candidate genes. In vitro experiments confirmed the differential expression of Arhgap31, Tm4sf1, Itm2a, and Vwa1 in senescent endothelial cells. Reduced expression of Arhgap31 attenuated endothelial cell senescence while enhancing migration and vasculogenesis capabilities. Arhgap31 may emerge as a potential target for ameliorating endothelial cell senescence and promoting tissue repair. Moreover, Connectivity Map analysis predicted several candidate compounds with expression profiles opposing the disease-associated signature, providing hypotheses for future pharmacological validation. Our findings highlight the contribution of endothelial cell senescence to post-ischemic endothelial dysfunction and inflammatory remodeling, supporting further investigation of this process in ischemic stroke pathogenesis. This work provides crucial insights into the interplay between cellular senescence and cerebrovascular disease, opening new avenues for precision medicine interventions in ischemic stroke management.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"26 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838214","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}