Frontiers in Cell and Developmental Biology最新文献

{"title":"Nauclea officinalis extract rescues working memory deficits in adolescent maternal immune activation offspring by restoring cholinergic signaling.","authors":"Lei An, Zhanyong Li, Yan Wang, Lin Feng, Wei Sun","doi":"10.3389/fcell.2026.1918425","DOIUrl":"10.3389/fcell.2026.1918425","url":null,"abstract":"<p><strong>Objective: </strong>Maternal immune activation (MIA) is a key risk factor for schizophrenia-related cognitive deficits, linked to prefrontal cholinergic dysfunction. Nauclea officinalis extract (NOE) possesses documented anti-inflammatory and neuroprotective properties, but its effects on MIA-induced cognitive and neuronal dysfunctions are unknown. This study aimed to investigate whether NOE ameliorates MIA-induced working memory deficits by modulating infralimbic medial prefrontal cortex (IL-mPFC) cholinergic signaling and neuronal activity.</p><p><strong>Methods: </strong>Using a poly (I:C)-induced MIA rat model, adolescent offspring were treated with NOE (5, 10 and 20 mg/kg). Behavioral tests, <i>in vivo</i> electrophysiology, and molecular assays were conducted.</p><p><strong>Results: </strong>NOE dose-dependently attenuated MIA-induced neuroinflammation (IL-1β, IL-6, TNF-α) in the IL-mPFC. It restored acetylcholine (ACh) levels, reduced acetylcholinesterase (AChE) activity, but did not alter M1/M3 receptor expression. NOE (20 mg/kg) significantly improved 30-s delay working memory performance, an effect blocked by the muscarinic receptor antagonist scopolamine (SCO) and mimicked by the AChE inhibitor physostigmine (PHY). Electrophysiologically, NOE rescued MIA-impaired long-term potentiation (LTP) and paired-pulse ratio (PPR), and enhanced delay-related firing of IL pyramidal neurons. These restorative effects were similarly replicated by PHY and antagonized by SCO.</p><p><strong>Conclusion: </strong>NOE alleviates MIA-induced working memory deficits by reducing neuroinflammation and, crucially, by functionally potentiating cholinergic transmission in the IL-mPFC. The findings highlight the IL cholinergic system as a critical therapeutic target and position NOE as a promising multi-target agent for cognitive impairments in neurodevelopmental disorders.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1918425"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the inflammatory link: integrated analysis identifies BMP7 and PPBP as key genes in obstructive sleep apnea-related atrial fibrillation.","authors":"Feng Li, Xing Xu, Yi-Qiu Hu, Cheng-Peng Zhang, Yi-Wei Shen, Chi Geng, Jia-Peng Chu, Hui-Yu Bai, Xiao-Song Gu, Hui Li","doi":"10.3389/fcell.2026.1914540","DOIUrl":"10.3389/fcell.2026.1914540","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) is an independently modifiable risk factor for atrial fibrillation (AF). However, the molecular mechanism of OSA-related AF is elusive. This study aims to identify the key genes and pathophysiological changes underlying OSA-related AF.</p><p><strong>Methods: </strong>Three AF expression datasets, along with one OSA-related PBMC dataset and one OSA-related adipose tissue dataset, were acquired from the GEO database. DEG analysis and WGCNA were conducted to identify key AF-associated genes and OSA-related secretory proteins. PPI network analysis, functional enrichment, and cMAP were employed to uncover pathogenic genes, explore underlying mechanisms, and predict potential therapeutic compounds for OSA-related AF. LASSO regression and random forest were applied to screen candidate biomarkers and develop a diagnostic nomogram for OSA-related AF prediction. Immune cell infiltration in AF was assessed using the CIBERSORT algorithm. Finally, findings from bioinformatic analyses were validated through clinical cohort studies and animal model experiments.</p><p><strong>Results: </strong>The integrated AF dataset identified 123 AF key genes by intersecting differential expression and WGCNA. A total of 412 OSA-associated secretory proteins were screened by differential expression analysis of OSA-PBMC/adipose tissue datasets. PPI analysis identified two key modules containing 71 nodes, regarded as OSA-related AF pathogenic genes, which were mostly enriched in inflammatory and immune regulation by enrichment analysis. The cMAP analysis identified GW-9662 as a potential drug for OSA-related AF treatment. Six genes were overlapped between AF key genes and OSA-associated secretory proteins, and two hub genes were chosen as candidate biomarkers for developing nomogram with ideal diagnostic performance through machine learning. Immune cell infiltration results uncovered immune dysregulation in AF, and BMP7/PPBP were significantly associated with infiltrating immune cells. Finally, clinical and rat model validation confirmed that PPBP was upregulated and BMP7 downregulated in OSA with AF. A nomogram incorporating these genes showed good diagnostic performance (AUC = 0.843), and OSA rats exhibited increased AF susceptibility, fibrosis, and inflammation.</p><p><strong>Conclusion: </strong>This study suggests that the downregulated BMP7 and upregulated PPBP may serve as key molecular features in the pathogenesis of OSA-related AF, highlighting a shared pathological pathway between OSA and AF.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1914540"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on the function of non-muscle myosin II during cell division.","authors":"Jingjing Ding","doi":"10.3389/fcell.2026.1852038","DOIUrl":"10.3389/fcell.2026.1852038","url":null,"abstract":"<p><p>Myosin is a superfamily of motor proteins that has attracted extensive research interest for many years due to its ability to efficiently convert chemical energy into mechanical energy during muscle contraction and various other movements in eukaryotic cells. Non-muscle myosin II (NMII) consists of three members, NMIIA, NMIIB, and NMIIC, which are positioned at the downstream end of numerous signaling pathways and plays a central role in cell adhesion, migration, and division. During cell division, NMII serves as the primary protein that generates mechanical force. It participates not only in cell rounding from prophase to metaphase but also interacts with actin to assemble a contractile ring during late stages, which then contracts to split the mother cell into two daughter cells. Loss of NMII function may result in cell division failure and consequently tetraploidy. Subsequent division of tetraploid cells can generate aneuploidy, which is closely associated with tumorigenesis as shown in many studies. In this review, we will discuss the roles of NMII throughout the entire cell division cycle.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1852038"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geometric mechanogenomics: engineering boundary conditions for deterministic cell fate control.","authors":"Mohsen Taghizadeh, Ali Taghizadeh, Hye Sung Kim","doi":"10.3389/fcell.2026.1922536","DOIUrl":"10.3389/fcell.2026.1922536","url":null,"abstract":"<p><p>In tissue development and regeneration, cellular behavior has traditionally been interpreted through biochemical signaling frameworks. However, cells exist within physically defined environments, where geometric boundary conditions - including confinement, curvature, anisotropy, and multicellular architecture - define the mechanical state space in which mechanical forces are generated, transmitted, and interpreted. Here, we introduce geometric mechanogenomics, a conceptual framework that positions geometry as an upstream spatial regulator linking tissue-scale boundary conditions to nuclear mechanics, chromatin organization, and genome regulation. We propose a boundary-to-nucleus axis through which geometric information is decoded by adhesion-mediated mechanotransduction, cytoskeletal force transmission, and nuclear mechanoregulation to regulate chromatin accessibility, epigenetic remodeling, and transcriptional programs. Rather than introducing new mechanotransduction pathways, this framework emphasizes that geometry spatially organizes conserved mechanotransductive machinery to generate context-dependent mechanogenomic outcomes. We further discuss how engineered geometries reduce morphogenetic stochasticity, coordinate multicellular organization, and establish mechanical memory that influences long-term cell fate. Finally, we highlight current challenges in establishing predictive geometry-to-genome relationships and discuss emerging opportunities enabled by spatial omics, artificial intelligence-assisted inverse design, and dynamic biomaterials for programmable mechanobiology, regenerative medicine, developmental biology, and disease modeling.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1922536"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context-dependent functions of the aryl hydrocarbon receptor in gastrointestinal cancers: from microenvironmental regulation to precision targeted therapy.","authors":"Jiao Ma, Shenghao Li, Yining Qiao, Zihan Gao, Jinzhe Liu, Yanru Song, Yu Liu, Xiaohui Ji, Jianbo Li, Jie Zhang, Liang Chang, Bingjie Huo","doi":"10.3389/fcell.2026.1886657","DOIUrl":"10.3389/fcell.2026.1886657","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with context-dependent roles in gastrointestinal (GI) tumor development. Depending on cellular context and microenvironment, AhR can preserve epithelial integrity, suppress inflammation, and inhibit tumor growth, but it can also promote immune evasion and metabolic reprogramming to drive tumor progression. Most existing reviews have focused on a single GI tumor type or functional dimension, and the concept of AhR as a context-dependent signaling hub has not been effectively linked to therapeutic stratification across the full spectrum of GI malignancies. No prior review has systematically compared AhR across five GI cancer types-esophageal, gastric, colorectal, hepatocellular, and pancreatic-or addressed the translational gap between preclinical data and clinical application. This review addresses these gaps in three key ways. First, it provides the first head-to-head comparative analysis of AhR functions across these five cancer types. Second, it adopts a functional stratification framework integrating five core mechanistic dimensions-tumor stemness, epithelial-mesenchymal transition, immune remodeling, metabolic reprogramming, and drug resistance-and proposes a three-dimensional AhR stratification model. Third, it systematically discusses emerging AhR-targeted therapeutic strategies-including antagonists, selective AhR modulators (SAhRMs), PROTACs, combination therapies, and microbiome-based interventions-while critically evaluating translational challenges. By establishing this context-informed framework, we aim to provide a conceptual basis for biomarker-guided evaluation of AhR-targeted strategies in GI cancers.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1886657"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging regulated cell death (cuproptosis, disulfidptosis, and PANoptosis) in ischemic stroke: research progress and translational prospects.","authors":"Dongyang Xing, Ke Xiang","doi":"10.3389/fcell.2026.1893238","DOIUrl":"10.3389/fcell.2026.1893238","url":null,"abstract":"<p><p>Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. Its pathological mechanisms involve complex cascades including energy metabolism failure, excitotoxicity, oxidative stress, neuroinflammation, and multiple forms of regulated cell death (RCD). In recent years, cuproptosis, disulfidptosis, and PANoptosis, as three emerging RCD modalities, have attracted increasing attention in ischemic brain injury. Cuproptosis is triggered by copper overload and leads to proteotoxic stress via abnormal oligomerization of lipoylated mitochondrial proteins. Disulfidptosis occurs under glucose deprivation combined with high SLC7A11 expression, driven by NADPH depletion and intracellular disulfide stress that collapses the actin cytoskeleton. PANoptosis integrates pyroptosis, apoptosis, and necroptosis through the PANoptosome-a multiprotein platform assembled by innate immune sensors (ZBP1, AIM2, NLRP3) together with adaptor proteins (ASC, FADD) and effectors (caspase-1/8, RIPK3, MLKL, GSDMD)-leading to simultaneous execution of all three death programs and amplified neuroinflammatory injury. These three death modalities exhibit marked cell-type heterogeneity across neurons, microglia, astrocytes, and endothelial cells within the neurovascular unit, and converge on shared hubs of oxidative stress, mitochondrial dysfunction, and inflammatory signaling, forming a complex inter-pathway crosstalk network. This review systematically summarizes the molecular mechanisms, cellular specificity, spatiotemporal dynamics, and inter-pathway crosstalk of these three emerging RCDs in ischemic stroke, and discusses the clinical translational prospects of targeted and combination intervention strategies-including a stage-classified analysis of therapeutic candidates from preclinical to clinical development-providing a theoretical basis for the design of novel neuroprotective agents.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1893238"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 transcriptomic and experimental analyses prioritize TPT1 as a PANoptosis-associated candidate molecular marker in sarcopenia.","authors":"Shijie Dong, Min Wang, Chen Liang, Peiyu Xu, Ziyi Ye, Jingqing Yao, Zhongquan Tang, Ting Ou, Xiaomin Zhao, Xinyu Dai, Yuntao Li, Guozhong Ji","doi":"10.3389/fcell.2026.1912393","DOIUrl":"10.3389/fcell.2026.1912393","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sarcopenia lacks sensitive molecular markers for early detection, and its relationship with integrated inflammatory cell-death programs remains unclear. PANoptosis integrates apoptotic, pyroptotic, and necroptotic signaling and therefore provides a plausible framework for investigating inflammatory-stress remodeling in aging skeletal muscle.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We integrated four bulk-transcriptomic datasets from the Gene Expression Omnibus into a training cohort (66 controls; 37 sarcopenia) and used GSE111016 as an external validation cohort (20 controls; 20 sarcopenia). We intersected differentially expressed genes with a curated PANoptosis-associated gene set and then performed enrichment analysis; least absolute shrinkage and selection operator (LASSO), random forest and extreme gradient boosting (XGBoost) feature selection; nomogram and receiver operating characteristic (ROC) analyses; CIBERSORT immune-cell deconvolution; and single-nucleus RNA sequencing (snRNA-seq) reanalysis. We assessed tumor protein, translationally controlled 1 (TPT1) expression in D-galactose-treated mouse and C2C12 models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 608 differentially expressed genes, 47 overlapped with the curated PANoptosis-associated gene set. These genes were enriched in apoptotic signaling; cytokine, nuclear factor kappa B (NF-κB), tumor necrosis factor (TNF), and nucleotide-binding oligomerization domain (NOD)-like receptor pathways; regulated necrosis; extracellular-matrix remodeling; and impaired oxidative phosphorylation. Three machine-learning algorithms converged on neurotrophic receptor tyrosine kinase 1 (NTRK1), TPT1, and TNF receptor-associated protein 1 (TRAP1). TPT1 showed the strongest single-gene discrimination, with areas under the ROC curve of 0.819 (95% confidence interval [CI], 0.737-0.900) in the training cohort and 0.753 (95% CI, 0.598-0.907) in the external cohort. Immune-cell deconvolution linked the candidate genes to estimated mast-cell, plasma-cell, cluster of differentiation 8-positive (CD8&lt;sup&gt;+&lt;/sup&gt;) T-cell, and macrophage proportions. Single-nucleus analysis of 97,154 nuclei from 17 donors showed broad TPT1 expression across myonuclear, satellite-cell, stromal, endothelial, and immune compartments, with lower expression in older muscle. Network and gene set variation analyses associated lower TPT1 expression with inflammatory, oxidative-stress, cell-death, and stress-adaptive pathways. In D-galactose-treated mice and C2C12 myotubes, muscle-wasting or senescence-like changes coincided with lower TPT1 protein abundance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study prioritizes TPT1 as a candidate molecular marker associated with the bulk-transcriptomic sarcopenia phenotype. The aging-muscle and D-galactose analyses provide biological context but do not establish sarcopenia specificity or causality. Prospective clinical validation and functional perturbation studies are required.&lt;/p","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1912393"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the causal impact of gut microbiota on periodontitis based on Mendelian randomization, bulk transcriptomics, and single-cell transcriptomics.","authors":"Huiru Li, Runze Kong, Ping Chang, Fangyi Xie, Tianxiao Zhu, Yang Xie","doi":"10.3389/fcell.2026.1884760","DOIUrl":"10.3389/fcell.2026.1884760","url":null,"abstract":"<p><strong>Background: </strong>Dysbiosis of the gut microbiota is closely associated with periodontitis (PD), yet whether a direct causal relationship exists and the underlying molecular mechanisms remain unclear. This study aims to identify key genes linking gut microbiota to PD, providing molecular targets for its precise prevention, diagnosis, and treatment.</p><p><strong>Methods: </strong>Three PD-related transcriptomic datasets (GSE10334, GSE223924, GSE171213) were obtained from public databases. Through Mendelian randomization (MR), machine learning, and expression validation, key regulatory genes causally linking gut microbiota to PD were identified. Gingival tissue specimens from PD patients (n = 6) and healthy controls (n = 6) were used for independent validation via quantitative real-time PCR(qRT-PCR) and Western blot. Immune cell infiltration analysis and cell communication network analysis were further conducted using single-cell RNA sequencing data.</p><p><strong>Results: </strong>MR analysis identified 22 gut microbiota taxa causally associated with PD (12 protective, OR<1; 10 risk-associated, OR>1). Transcriptomic analysis yielded seven candidate genes, which were narrowed to 4 feature genes via multi-algorithm machine learning. Cross-dataset validation confirmed three key genes-IL-19, NID2, and SH3D19-with consistent differential expression. Independent experimental validation confirmed significant upregulation of NID2 at both mRNA and protein levels in the PD group (<i>P</i> < 0.01), while IL-19 and SH3D19 showed no statistically significant differences. Immune infiltration analysis revealed increased plasma cell infiltration and decreased CD8⁺ T cell infiltration in PD (<i>P</i> < 0.05). Single-cell communication analysis showed that in controls, monocyte-neutrophil interactions predominated, whereas in PD, interactions along the monocyte/MDSC/neutrophil axis were additionally elevated.</p><p><strong>Conclusion: </strong>This multi-omics study identified 22 gut microbiota taxa causally associated with PD, and IL-19, NID2, and SH3D19 as key dysregulated genes. Among these, NID2 emerged as a prioritized candidate linking gut dysbiosis to periodontitis, warranting further functional investigation. These findings provide molecular evidence for the oral-gut axis and offer potential biomarkers and therapeutic targets for PD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1884760"},"PeriodicalIF":5.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide CRISPR screen identifies RNF24 as a critical host factor for foot-and-mouth disease virus entry.","authors":"Jinyan Zhang, Hailong Liu, Jian Du, Min Zhang, Mengge Yin, Qiongqiong Zhao, Xinghua Chen, Xiangmin Li, Zengjun Lu, Shengsong Xie, Ping Qian","doi":"10.3389/fcell.2026.1909904","DOIUrl":"10.3389/fcell.2026.1909904","url":null,"abstract":"<p><strong>Background: </strong>Foot-and-mouth disease virus (FMDV) causes substantial economic losses in global livestock production; however, the key host factors supporting its early infection process remain poorly characterized.</p><p><strong>Methods: </strong>In this study, we performed an unbiased genome-wide CRISPR/Cas9 knockout screening using porcine cells to screen and identify host factors involved in FMDV infection.</p><p><strong>Results: </strong>We identified that the E3 ubiquitin ligase RNF24 supports efficient FMDV entry. RNF24 depletion inhibits viral entry and replication, whereas its overexpression enhances viral infectivity. Mechanistically, RNF24 preferentially promotes K27-linked non-degradative polyubiquitination of leupaxin (LPXN) at lysine 162, driving LPXN's trafficking to the plasma membrane. At the membrane, LPXN assembles a ternary integrin-LPXN-VP1 complex that strengthens virus-receptor interactions and promotes viral adsorption and entry. Disruption of this ubiquitination event via the LPXN K162R mutation impairs complex formation and compromises viral entry.</p><p><strong>Conclusion: </strong>Together, our study reveals a ubiquitin-dependent RNF24-LPXN regulatory axis that supports FMDV entry, highlights the role of non-degradative ubiquitination in viral pathogenesis, and proposes this interface as a potential target for antiviral intervention.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1909904"},"PeriodicalIF":5.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling novel insights into gene expression in monkey testes through single-nucleus-based analysis.","authors":"Yu Zhang, Shu Wei, Runqing Zou, Yuxin Li, Nianfeng Jiang, Zhao Li, Chao Ma, Yun Wang, Jin Ben, Longbao Lv, Fang Yan","doi":"10.3389/fcell.2026.1930189","DOIUrl":"10.3389/fcell.2026.1930189","url":null,"abstract":"<p><strong>Background: </strong>Spermatogenesis is a highly intricate and tightly regulated process that involves the coordinated interplay of various cell types. Understanding the expression profiles of individual cells is crucial for unraveling the intricacies of spermatogenesis. This study aimed to uncover novel gene expression patterns and regulatory features during primate spermatogenesis.</p><p><strong>Methods: </strong>We performed single-nucleus RNA sequencing on testicular tissues from cynomolgus macaques at four developmental stages (infancy, puberty, adulthood, and aged). To explore chromatin regulatory landscapes, we also conducted single-nucleus ATAC sequencing on pubertal testes. We integrated both datasets and applied clustering, differential expression analysis, gene ontology enrichment, pseudo time trajectory reconstruction, and transcription factor motif enrichment to characterize cell types, differentiation trajectories, and cell-type-specific regulatory programs.</p><p><strong>Results: </strong>Our integrated analysis comprehensively characterized all major germ and somatic cell types, including a previously unrecognized quiescent undifferentiated spermatogonial (uSPG) subtype in early spermatogenesis that exhibits a transcriptomic state distinct from canonical type A spermatogonial stem cells, which we provisionally term as uSPG1. We also revealed the differentiation states, and expression and function of genes within distinct cell types during spermatogenesis. Notably, we found that classic niche factors essential for spermatogonial stem cell maintenance, including <i>GDNF</i>, <i>FGF2</i>, and <i>CXCL12</i>, were not readily detected in Sertoli cells by snRNA-seq. Instead, their transcripts were predominantly observed in myoid cells or germ cells, a pattern corroborated by both transcriptomic and chromatin accessibility data. This observation, pending further experimental validation, suggests a need for reevaluation of the cellular sources of these critical niche signals in primates.</p><p><strong>Conclusion: </strong>These findings offer a refined single-nucleus-resolution view of primate spermatogenesis, revealing a novel undifferentiated germ cell state and emphasizing the need for further exploration of Sertoli cells in male reproductive biology. Our results underscore the power of combined single-nucleus RNA and ATAC sequencing for investigating complex reproductive tissues. This research enhances our understanding of the intricate mechanisms governing spermatogenesis and may offer new perspectives on male fertility regulation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1930189"},"PeriodicalIF":5.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}