Frontiers in Genetics最新文献

{"title":"Regulation of term and preterm labor: genetics and epigenetics.","authors":"Kaiyi Sun, Ning Wang, Yuanyuan Liu, Lu Gao","doi":"10.3389/fgene.2025.1594030","DOIUrl":"10.3389/fgene.2025.1594030","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1594030"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553369","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":"Data simulation to optimize frameworks for genome-wide association studies in diverse populations.","authors":"Jacquiline W Mugo, Nicola Mulder, Emile R Chimusa","doi":"10.3389/fgene.2025.1559496","DOIUrl":"10.3389/fgene.2025.1559496","url":null,"abstract":"<p><p>Whole-genome or genome-wide association studies (GWAS) have become a fundamental part of modern genetic studies and methods for dissecting the genetic architecture of common traits based on common polymorphisms in random populations. It is hoped that there would be many potential uses of these identified variants, including a better understanding of the pathogenesis of traits, disease risk prediction, discovery of biomarkers, and clinical prediction of drug treatments for populations and global health. Questions have been raised about whether associations that are largely discovered in European ancestry populations are replicable in diverse populations, can inform medical decision-making globally, and how efficiently current GWAS tools perform in populations of high genetic diversity, multi-wave genetic admixture, and low linkage disequilibrium, such as African populations. Here, we discuss some of the challenges in association mapping and leverage genomic data simulation to mimic structured African, European, and multi-way admixed populations to evaluate the replicability of association signals from current state-of-the-art GWAS tools. We use the results to discuss optimized frameworks for the analysis of GWAS data in diverse populations. Finally, we outline the implications, challenges, and opportunities these studies present for populations of non-European descent.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1559496"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553352","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":"Integrative bioinformatics analysis and experimental validation reveals key genes and regulatory mechanisms in the development of gout.","authors":"Ye Yuan, Zhiqiang Gao, Jianhong Chen, Yuejing Liu, Jingguo Zhou","doi":"10.3389/fgene.2025.1598835","DOIUrl":"10.3389/fgene.2025.1598835","url":null,"abstract":"<p><strong>Background and aims: </strong>Gout is a prevalent inflammatory arthropathy caused by monosodium urate crystal deposition, yet its molecular pathogenesis remains incompletely understood. This study aimed to identify key genes and elucidate regulatory mechanisms underlying gout development through bioinformatics analysis combined with experimental validation.</p><p><strong>Methods: </strong>Transcriptome dataset GSE160170 and single-cell dataset GSE211783 were analyzed using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Functional enrichment, protein-protein interaction (PPI), ceRNA, and transcription factor networks were constructed. Immune cell infiltration was analyzed using CIBERSORTx. Molecular docking predicted therapeutic compounds. Experimental validation included qRT-PCR, Western blot, gene knockdown/overexpression, and functional assays.</p><p><strong>Results: </strong>Among 329 gout-related genes identified, CXCL8, PTGS2, and IL10 emerged as key regulators involved in cell-cell adhesion, leukocyte activation, and NF-κB signaling. Immune infiltration revealed significant upregulation of M2 macrophages, activated mast cells, activated NK cells, and γδ T cells in gout samples. CeRNA network identified KCNQ1OT1 and hsa-mir-98-5p as regulatory elements, while CEBPB, STAT3, RELA, and NFKB1 were key transcription factors. Molecular docking suggested pergolide as a therapeutic candidate. Single-cell analysis confirmed high expression of key genes in T/NK cells and myeloid cells. Western blot validation showed upregulated protein expression of key genes in the gout model. PTGS2 knockdown enhanced cell viability and reduced apoptosis, while overexpression promoted inflammatory cytokine production and NF-κB pathway activation.</p><p><strong>Conclusion: </strong>This study systematically elucidated the pivotal roles of CXCL8, PTGS2, and IL10 in gout pathogenesis, providing valuable molecular targets for therapeutic development.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1598835"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553367","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 xyloglucan endotransglucosylase/hydrolase gene, <i>IbXTH16</i>, increases cold tolerance in transgenic sweetpotato.","authors":"Tao Yu, Jiaquan Pan, Sitong Liu, Zitong Yang, Zhenlei Liu","doi":"10.3389/fgene.2025.1629260","DOIUrl":"10.3389/fgene.2025.1629260","url":null,"abstract":"<p><strong>Introduction: </strong>Low temperature is a key environmental factor that threaten sweetpotato growth and development. In-depth studies on the gene functions underlying cold resistance are important for genetic engineering in sweetpotato.</p><p><strong>Methods: </strong>The <i>IbXTH16</i> gene was cloned using a homologous cloning approach. Its expression was detected in sweetpotato leaves subjected to low-temperature stress and brassinosteroid treatment. Subsequently, the <i>IbXTH16</i> gene was introduced into sweetpotato variety Lizixiang to generate <i>IbXTH16</i>-overexpressing plants, thereby enabling the functional validation of the <i>IbXTH16</i>.</p><p><strong>Results and discussion: </strong>The <i>IbXTH16</i> gene was cloned from the cold-tolerant variety LHS21. Its 879 bp coding sequence encoded a 292 aa protein with a molecular weight of 32.983 kDa and a pI of 8.47. The 2039 bp genomic sequence of <i>IbXTH16</i> contained two exons and one intron. The IbXTH16 protein was localized in the cell membrane. <i>IbXTH16</i> was strongly induced by 4°C and brassinosteroid. <i>IbXTH16</i> positively regulates cold tolerance of sweetpotato by activating the BR and proline pathways.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1629260"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553346","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":"Clinical characteristics and genetic mutation analysis in 18 pediatric patients with Shwachman-Diamond syndrome.","authors":"Ruoying Wei, Kaihui Zhang, Chen Liu, Xuxia Wei, Qin Jiang, Ji-An Li, Meiling Huo, Yinggang Liu, Mohnad Abdalla, Li-An Du, Xiaomei Yang, Fu Li","doi":"10.3389/fgene.2025.1603782","DOIUrl":"10.3389/fgene.2025.1603782","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the clinical features and genetic mutation spectrum of 18 children with Shwachman-Diamond syndrome (SDS).</p><p><strong>Methods: </strong>Data from 18 children with SDS at Shandong University Affiliated Children's Hospital (Ji'nan Children's Hospital) between April 2016 and June 2024 were retrospectively analyzed. Variant sites were confirmed by Sanger sequencing in family lines.</p><p><strong>Results: </strong>Patients exhibited complex and diverse clinical symptoms, often involving multiple systems. The clinical features of this cohort included (1) early onset (median age: 1.5 months), diarrhea, trypsin reduction, neutropenia, and growth retardation and (2) high incidence of pancreatic imaging abnormalities, bone marrow hypoplasia, developmental malformations, and neurocognitive disorders. All patients had homozygous or compound heterozygous <i>SBDS</i> mutations, with 258+2T>C identified as the hotspot mutation (20/37), while 41A>T and 185A>C were newly discovered mutations.</p><p><strong>Conclusion: </strong>Patients with SDS exhibit clinical heterogeneity, and this study enriches the <i>SBDS</i> gene mutation spectrum. Genetic testing is valuable for early diagnosis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1603782"},"PeriodicalIF":2.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553351","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":"Transcriptomic analysis and machine learning modeling identifies novel biomarkers and genetic characteristics of hypertrophic cardiomyopathy.","authors":"Feng Zhang, Chunrui Li, Lulu Zhang","doi":"10.3389/fgene.2025.1596049","DOIUrl":"10.3389/fgene.2025.1596049","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to leverage bioinformatics approaches to identify novel biomarkers and characterize the molecular mechanisms underlying hypertrophic cardiomyopathy (HCM).</p><p><strong>Methods: </strong>Two RNA-sequencing datasets (GSE230585 and GSE249925) were obtained from the Gene Expression Omnibus (GEO) repository. Computational analysis was performed to compare transcriptomic profiles between normal cardiac tissues from healthy donors and myocardial tissues from HCM patients. Functional annotation of differentially expressed genes (DEGs) was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Immune cell infiltration patterns were quantified via single-sample gene set enrichment analysis (ssGSEA). A predictive model for HCM was developed through systematic evaluation of 113 combinations of 12 machine-learning algorithms, employing 10-fold cross-validation on training datasets and external validation using an independent cohort (GSE180313).</p><p><strong>Results: </strong>A total of 271 DEGs were identified, primarily enriched in multiple biological pathways. Immune infiltration analysis revealed distinct patterns of immune cell composition. Based on the top differentially expressed genes, a robust 12-gene diagnostic signature (COMP, SFRP4, RASD1, IL1RL1, S100A8, S100A9, ESM1, CA3, MYL1, VGLL2, MCEMP1, and MT1A) was constructed, demonstrating superior performance in both training and testing cohorts.</p><p><strong>Conclusion: </strong>This study utilized bioinformatics approaches to analyze RNA-sequencing datasets, identifying DEGs and distinct immune infiltration patterns in HCM. These findings enabled the construction of a 12-gene diagnostic signature with robust predictive performance, thereby advancing our understanding of HCM's molecular biomarkers and pathogenic mechanisms.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1596049"},"PeriodicalIF":2.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539988","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":"Case Report: Successful late-line pralsetinib treatment in an ALK-rearranged lung adenocarcinoma patient with KIF5B-RET fusion resistant to alectinib.","authors":"Feng Jin, Chenyang Wang, Fang Yang, Shubin Wang, Fen Wang","doi":"10.3389/fgene.2025.1569912","DOIUrl":"10.3389/fgene.2025.1569912","url":null,"abstract":"<p><p>Anaplastic lymphoma kinase (<i>ALK</i>) fusion, an oncogenic driver alteration, accounts for 5%-6% of non-small cell lung cancer (NSCLC) patients. <i>ALK</i> tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in advanced ALK-rearranged NSCLC. However, acquired resistance to <i>ALK</i> TKIs inevitably arises, and the underlying mechanisms remain incompletely elucidated. This report describes a stage IV lung adenocarcinoma (LUAD) patient with <i>ALK</i>-rearranged who developed <i>KIF5B-RET</i> fusion-mediated resistance following second-line alectinib therapy. The patient achieved a partial response (PR) to third-line pralsetinib, sustained for 4 months. This case highlights <i>KIF5B-RET</i> fusion as a potential resistance mechanism post alectinib treatment and suggested = pralsetinib, a <i>RET</i> inhibitor, as a viable therapeutic option in this context. These findings contribute to the evolving understanding of resistance management strategies in <i>ALK</i>-rearranged NSCLC.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1569912"},"PeriodicalIF":2.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539987","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":"Genetic mutation and blue rubber bleb nevus syndrome: case reports and literature review.","authors":"Yueyi Xing, Han Liu, Hua Liu, Xueli Ding, Xue Jing","doi":"10.3389/fgene.2025.1516562","DOIUrl":"10.3389/fgene.2025.1516562","url":null,"abstract":"<p><p>Blue Rubber Bleb Nevus Syndrome (BRBNS) (OMIM %112200), or Bean syndrome, is an infrequent disorder characterized by venous malformations (VaMs) involving various organs such as the skin and gastrointestinal tract. Genetic mutations that affect the proliferation, migration, adhesion, differentiation, and survival of endothelial cells and the integrity of the extracellular matrix may be the pathogenesis of these disorders. We are supposed to investigate the cytogenetic results of BRBNS and report two sporadic cases. Two unrelated cases with BRBNS were from the Affiliated Hospital of Qingdao University and the First Affiliated Hospital of the University of South China, respectively. The data collection included information on the current age, sex, and race of the individuals, as well as their chief complaint. Clinical and family history, physical and laboratory findings, diagnostic workup, results, treatment, and complications were all documented. We are supposed to investigate the cytogenetic results of BRBNS and report two sporadic cases. We identified TEK missense mutations (c.596A>C) in both participants with BRBN. In addition, the mutation has appeared in <i>MMP9, NOTCH3, PRSS1, PDGFRA, CCM2, TSC2</i>, and <i>TNFAIP6</i>. KEGG pathway analysis showed that they participated in the PI3K-AKT signaling pathway. Our findings underscore the importance of exploring these genetic alterations in the context of BRBNS, which may have implications for developing targeted therapeutic approaches. We present two cases diagnosed with Bean syndrome, detailing their clinical features and molecular aspects.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1516562"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527577","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":"The joint role of the immune microenvironment and N⁷-methylguanosine for prognosis prediction and targeted therapy in acute myeloid leukemia.","authors":"Zhixiang Chen, Zhimei Chen, Xiaobo Huang, Xiongbin Yan, Xiaolin Lai, Shaoyuan Wang","doi":"10.3389/fgene.2025.1540992","DOIUrl":"10.3389/fgene.2025.1540992","url":null,"abstract":"<p><strong>Background: </strong>The tumor immune microenvironment (TIME) and N⁷-methylguanosine (m7G) modification play crucial roles in the progression of acute myeloid leukemia (AML). This study aims to establish an IME-related and m7G-related prognostic model for improved risk stratification and personalized treatment in AML.</p><p><strong>Methods: </strong>Immune score for the Cancer Genome Atlas acute myeloid leukemia (AML) patients were calculated using the ESTIMATE algorithm, followed by identification of immune score-associated differentially expressed genes Non-negative matrix factorization (NMF) clustering was performed to stratify AML subtypes based on immune microenvironment (immune microenvironment)-related DEGs and 29 m7G regulatory genes. Intersecting DEGs co-linked to IME and m7G features were analyzed through weighted gene co-expression network analysis Weighted correlation network analysis combined with univariate Cox, LASSO, and multivariate Cox regression to establish a prognostic signature. Biological pathway disparities between risk subgroups were analyzed via Gene Set Enrichment Analysis, Gene Set Variation Analysis, and ssGSEA. A clinical nomogram integrating the signature with prognostic indicators was developed. The expression of the 12 prognostic genes were tested and compared in AML and healthy donors. Drug sensitivity predictions for high-risk patients were generated using oncoPredict, supported by molecular docking simulations of ligand-target interactions and <i>in vitro</i> validation of candidate compounds in AML cell models.</p><p><strong>Results: </strong>We constructed an IMEm7G prognostic signature comprising 12 genes (MPZL3, TREML2, PTP4A3, AHCYL1, CBR1, REEP5, PPM1H, WDFY3, LAMC3, KCTD1, DDIT4, KBTBD8) that robustly stratified AML risk and predicted survival in multiple cohorts. The high- and low-risk subgroups exhibited divergent biological pathways, mutational landscapes, immune infiltration patterns, immune checkpoint expression, and HLA profiles. This signature further guided therapeutic selection, with dactolisib identified as a high-risk-specific candidate. The quantitative real-time PCR (qPCR) analysis demonstrated that in comparison with healthy donors, the expression of WDFY3, PPM1H, and REEP5 was significantly lower, while that of PTP4A3, AHCYL1, CBR1, MPZL3, TREML2, and KBTBD8 was higher in AML patients. <i>In vitro</i> CCK-8 assays validated dactolisib's monotherapy efficacy and synergistic cytotoxicity when combined with doxorubicin in AML cells.</p><p><strong>Conclusion: </strong>The IMEm7G gene signature established in our study effectively optimized the risk classification and predicted immunotherapy response in AML. Moreover, dactolisib was identified and demonstrated cytostatic activity alone and synergistic effects with doxorubicin in AML cells.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1540992"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527579","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":"Reduced T-Cell stemness underlies Th17 expansion and graft dysfunction in kidney transplant recipients.","authors":"Chang Liu, Hao Jiang, Andu Zhu, Chen Xu, Zhenfan Wang, Guocai Mao, Minjun Jiang, Jianchun Chen, Zheng Ma, Jiaqian Qi, Zhijun Cao","doi":"10.3389/fgene.2025.1588941","DOIUrl":"10.3389/fgene.2025.1588941","url":null,"abstract":"<p><strong>Introduction: </strong>End-stage renal disease (ESRD) is increasing worldwide, and although kidney transplantation improves survival, long-term graft loss-driven mainly by immune-mediated rejection-remains common. We aimed to delineate immune mechanisms that distinguish recipients with stable versus impaired graft function.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells from kidney-transplant recipients with normal (n = 10) or impaired (n = 10) renal function were profiled by single-cell RNA sequencing. Fourteen immune populations were identified; CD4⁺ T-cell \"stemness\" was quantified using mRNAsi and EREG_mRNAsi indices, lineage trajectories were reconstructed with Monocle, and ligand-receptor communication was inferred with iTalk. Findings were validated in an independent bulk RNA-seq cohort (n = 192) using differential expression and weighted gene co-expression network analysis (WGCNA).</p><p><strong>Results: </strong>Recipients with graft dysfunction exhibited (i) expansion of Th17 cells and contraction of Treg cells, (ii) significant loss of CD4⁺ T-cell stem-like features (lower mRNAsi/EREG_mRNAsi, p < 0.001), and (iii) pseudotime trajectories skewed toward Th17 differentiation. iTalk revealed enhanced S100A8/A9-TLR4 signalling from myeloid cells to neutrophils, consistent with reduced circulating neutrophils and presumptive intragraft accumulation. Bulk validation confirmed the stemness deficit and identified eight hub genes (API5, CAPRIN1, CCT2, DLG1, NMD3, RDX, SENP7, S100A4) that correlated with both low stemness and poor clinical outcome. Pathway enrichment implicated cell-morphogenesis, tight-junction, and metabolic-homeostasis pathways in graft injury.</p><p><strong>Discussion: </strong>Integrative single-cell and bulk analyses link diminished CD4⁺ T-cell stemness, Th17-dominant polarization, and S100A4-mediated neutrophil recruitment to graft dysfunction. These signatures nominate stemness indices, Th17/Treg balance, and the S100-TLR4 axis as candidate biomarkers and therapeutic targets to preserve allograft integrity and prolong transplant survival.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1588941"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527578","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}