Frontiers in Cell and Developmental Biology最新文献

{"title":"Integrated pathogen detection and immune profiling in posner-schlossman syndrome: a metagenomic and cytokine approach.","authors":"Dongqing Yuan, Chenfeng Gu, Yuan Fang, Qin Yang","doi":"10.3389/fcell.2026.1918795","DOIUrl":"10.3389/fcell.2026.1918795","url":null,"abstract":"<p><strong>Background: </strong>Posner-Schlossman syndrome (PSS) is recurrent unilateral anterior uveitis with severely elevated intraocular pressure disproportionate to visible inflammation. Cytomegalovirus (CMV) is linked to partial PSS cases, yet it is unknown whether CMV induces unique immune signatures or only amplifies baseline inflammation. We combined metagenomic next-generation sequencing (mNGS), multiplex cytokine detection and machine learning to clarify CMV's pathogenic role.</p><p><strong>Methods: </strong>This single-center prospective study recruited 52 untreated patients with acute PSS and 25 sex-matched cataract controls. Aqueous humor samples underwent mNGS pathogen testing to divide PSS patients into CMV-positive and CMV-negative groups, and cytometric bead array was used to quantify 9 immune mediators. Seven machine learning algorithms covering linear, kernel, ensemble tree, probabilistic and discriminant models were applied to distinguish CMV status, with XGBoost and LightGBM added to validate result stability. All models were built in Python 3.9.</p><p><strong>Results: </strong>mNGS identified CMV in 42.3% of PSS patients. Baseline clinical features were comparable between CMV subgroups. Six pro-inflammatory cytokines were significantly higher in PSS patients than controls, whereas no cytokine differed between CMV subgroups after Bonferroni correction. All seven models poorly discriminated CMV status; quadratic discriminant analysis yielded the maximum AUC of merely 0.552. SHAP values verified weak predictive power of cytokines, and learning curves indicated severe overfitting and limited generalizability within the evaluated range of training sample sizes.</p><p><strong>Conclusion: </strong>Within the current sample size and measured cytokine panel, no statistically significant or stable difference in aqueous cytokine profiles was detected between CMV-positive and CMV-negative PSS patients, even with advanced machine learning methods. Our findings are consistent with the inflammation amplifier hypothesis, but the current cross-sectional data cannot definitively confirm CMV's biological role, nor rule out CMV as a primary pathogenic trigger in a subset of PSS cases. Direct pathogen detection is required for personalized antiviral treatment, and shared inflammatory pathways provide universal targets for novel immunomodulatory therapies for all PSS patients.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1918795"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165046","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":"Single-cell RNA sequencing reveals PANoptosis signatures of acinar cells, macrophages, and neutrophils during injury and repair in acute pancreatitis.","authors":"Weizhi Zhang, Feng Cao","doi":"10.3389/fcell.2026.1948502","DOIUrl":"10.3389/fcell.2026.1948502","url":null,"abstract":"<p><strong>Background: </strong>Acute pancreatitis (AP) involves acinar cell injury, inflammation, and tissue remodeling. Although regulated cell death pathways contribute to AP progression, the cell type-specific features and dynamics of PANoptosis remain unclear. This study aimed to characterize PANoptosis-associated signatures in pancreatic cell populations at single-cell resolution.</p><p><strong>Methods: </strong>A caerulein plus lipopolysaccharide-induced mouse AP model was established. Pancreatic tissues from wild-type, AP, and early recovery groups were analyzed by single-cell RNA sequencing. Major cell types and subclusters were identified using marker genes. PANoptosis-related programs were evaluated using multiple scoring algorithms, pseudotime analysis, and functional enrichment. Histological and immunohistochemical analyses were performed for validation.</p><p><strong>Results: </strong>Single-cell profiling revealed extensive remodeling of the pancreatic cellular microenvironment during AP and recovery, characterized by acinar cell loss and increased macrophage and neutrophil infiltration. Acinar cell subclustering identified 12 transcriptionally distinct subpopulations, including injury-associated subsets with ductal-like features marked by Krt19, Epcam, Lcn2, and Krt7. Trajectory analysis suggested dynamic transitions from mature digestive enzyme-producing acinar states toward stress-associated and inflammatory states. PANoptosis-related signatures were most prominent in inflammatory acinar subsets, particularly Cluster 10, followed by Clusters 7, 4, and 5. Macrophage and neutrophil analyses further identified PANoptosis-high inflammatory subsets, especially macrophage Cluster 4 and neutrophil Cluster 4.</p><p><strong>Conclusion: </strong>This study establishes a single-cell atlas of AP injury and recovery, revealing cell-specific PANoptosis programs in acinar cells and inflammatory populations, highlighting PANoptosis as a potential link between acinar injury, immune activation, and pancreatic remodeling.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1948502"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165756","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":"Cancer-associated fibroblasts in head and neck tumours: signalling networks and therapeutic implications with insights from vestibular schwannoma.","authors":"Xiaoli Zhang","doi":"10.3389/fcell.2026.1927031","DOIUrl":"10.3389/fcell.2026.1927031","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are heterogeneous stromal cells that influence extracellular matrix (ECM) organisation, tumour-cell state, immunity, and treatment response in head and neck squamous cell carcinoma (HNSCC). This review synthesises evidence on CAF origins and states and on the transforming growth factor beta (TGF-β), Wnt/β-catenin, PI3K/AKT/mTOR, and Hippo-YAP/TAZ networks that mediate fibroblast interactions with tumour and immune cells. Vestibular schwannoma (VS) is considered only as a hypothesis-generating benign stromal reference: both tumours contain fibroblast and ECM-remodelling compartments, but differ fundamentally in cell of origin, anatomy, oncogenic drivers, immune context, and invasive behaviour. VS stromal fibroblasts are not designated as CAFs unless a study has explicitly applied that term, and cross-tumour observations are not treated as evidence of biological equivalence. Single-cell and spatial studies reveal multiple HNSCC fibroblast states, including myofibroblastic, inflammatory, antigen-presenting and fibroblastic reticular cell (FRC)-like, and immune-regulatory populations, but nomenclature and marker sets remain inconsistent and most inferred functions require perturbational validation. Translational evidence is similarly uneven: broad CAF depletion can be harmful in some non-HNSCC models, whereas pathway- or state-selective modulation is supported mainly by preclinical studies. Early HNSCC trials of TGF-β/programmed death-ligand 1 (PD-L1) blockade and NADPH oxidase 1/4 (NOX1/4) inhibition provide feasibility signals but not definitive efficacy. Current evidence supports biomarker-guided investigation of functionally defined CAF states; stromal observations in VS remain hypothesis-generating and require direct experimental validation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1927031"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171015","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":"The role of mitochondrial DNA and RNA in promoting liver disease pathogenesis.","authors":"Sanjeevani Raj, Anjali Warhade, Nikkee Kumari, Shweta Pandey, Mrigya Babuta","doi":"10.3389/fcell.2026.1855694","DOIUrl":"https://doi.org/10.3389/fcell.2026.1855694","url":null,"abstract":"<p><p>Mitochondria are a semi-autonomous organelle due to their unique structural organization and independent genetic system, and they play diverse roles in maintaining cellular homeostasis. The liver is the central metabolic organ and performs myriad functions, including energy production, metabolism, and detoxification. Liver diseases account for approximately two million mortalities per year. Mitochondrial dysfunction and damage are implicated in promoting the pathogenesis of different liver diseases. Mitochondria and mitochondrial nucleic acids, namely, mitochondrial DNA (mtDNA) and mitochondrial RNA (mtRNA), have emerged as regulators of innate immunity. Here, we first review the structural organization of mitochondria and the molecular mechanisms governing mitochondrial biogenesis, replication, and transcription. Next, we describe the mechanistic details by which mitochondrial dysfunction causes the release of mtDNA and mtRNA into the cytosol and extracellular milieu. Some of the mechanisms are through the opening of mitochondrial permeability transition pore (mPTP), voltage-dependent anion channel (VDAC) oligomerization, prohibitin (PHB1/2), mitochondria-derived vesicles (MDV), dysfunction of the mtRNA degradosomes, and senescence-associated secretory phenotype (SASP). Cell death pathways such as necrosis, necroptosis, and pyroptosis, in addition to perpetuating inflammation, also release mtDNA and mtRNA into the extracellular milieu. The released mtDNA and mtRNA act as damage associated molecular patterns (DAMPs) that engage various cytosolic DNA and RNA sensors and pattern recognition receptors (PRRs) such as cyclic guanosine-monophosphate-adenosine-monophosphate synthase (cGAS), toll-like receptor 9 (TLR9), toll-like receptor 3 (TLR3), Z-DNA-binding protein 1 (ZBP1), NOD-like receptor protein 3 (NLRP3), absent in melanoma 2 (AIM2), retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated protein 5 (MDA5), protein kinase R (PKR) and activate different signaling cascades downstream. This review provides a contemporary, comprehensive analysis of the available literature on the roles of mtDNA and mtRNA in liver diseases, including metabolic dysfunction-associated steatotic/steatohepatitis (MASLD/MASH), alcohol-associated liver disease (ALD), drug-induced liver injury (DILI), viral hepatitis, and hepatocellular carcinoma (HCC). Thus, the review highlights the potential of both mtDNA and mtRNA to serve as biomarkers of the pathological conditions of the liver, and the way the mitigation of mitochondrial dysfunction and the release of mtDNA or mtRNA can serve as potential therapeutic targets.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1855694"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180615","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":"Senomorphic miR-3155b suppresses the senescence-associated secretory phenotype in therapy-induced senescence.","authors":"Kunling Huang, Juan Chen, Yunying Liu, Chuyang Ding, Caiying Yi, Wenbin Ma, Su Wu, Feng Liu","doi":"10.3389/fcell.2026.1868137","DOIUrl":"10.3389/fcell.2026.1868137","url":null,"abstract":"<p><p>Senomorphic microRNAs (miRNAs) are a class of small regulatory RNAs that selectively suppress the senescence-associated secretory phenotype (SASP) without eliminating senescent cells, thereby offering a targeted approach to counteract the pro-tumorigenic consequences of therapy-induced senescence (TIS). Despite their therapeutic potential, senomorphic miRNAs in luminal breast cancer remain poorly characterized. Here, we performed small RNA sequencing to profile miRNA expression changes in a doxorubicin-induced TIS model using the luminal breast cancer line MCF7. We identified miR-3155b as a previously uncharacterized miRNA significantly downregulated during TIS. Functional studies revealed that miR-3155b overexpression suppressed the mRNA and protein levels of multiple SASP factors, including IL6, IL8 (CXCL8), MMP13, TNF, IL1B, and IFNB1, whereas its knockdown enhanced their expression. Critically, these effects occurred without affecting core senescence phenotypes such as proliferation arrest, SA-β-gal activity, or DNA damage foci formation. This senomorphic function was further confirmed in an ionizing radiation (IR)-induced TIS model and in T47D luminal breast cancer cells. miR-3155b was confirmed to target the <i>CXCL8</i> mRNA by luciferase reporter assays, and RNA pull-down assays indicated that miR-3155b physically associates with <i>IFNB1</i>, <i>IL6</i>, <i>TNF</i>, and <i>MMP13</i> mRNAs. Collectively, our findings identify miR-3155b as a senomorphic miRNA in Luminal A breast cancer TIS and provide a potential target for optimizing chemoradiotherapy strategies aimed at mitigating SASP-driven adverse effects.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1868137"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166295","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":"Secondary neurulation mechanisms likely arose in vertebrates during mesenchymal tailbud extension.","authors":"Daiki Sugita, Alexis Lauga, Martin Minařík, Lucy Barlow, Nicole Campbell, Michaela Vazačová, Martin Pšenička, Roman Franěk, Clare Buckley","doi":"10.3389/fcell.2026.1870085","DOIUrl":"https://doi.org/10.3389/fcell.2026.1870085","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The central nervous system (CNS) is an essential organ system common to all vertebrates and is one of the defining features of the Chordata phylum. In Chordates, neural tubes may form via either primary neurulation, secondary neurulation, or a mixture of the two. During primary neurulation, there is folding of an already-polarized epithelium. In contrast, secondary neurulation involves mesenchymal to epithelial transition, cell interdigitation and sometimes &lt;i&gt;de novo&lt;/i&gt; cavitation from an initially solid rod of mesenchymal cells. Current studies only show secondary neurulation in a subset of chordates, and it is unclear why this should be the case.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This article uses published literature to reevaluate the mode and the relative timings of neurulation and tailbud extension in chordate species. It also uses micro-computerized tomography (microCT) and immunohistochemistry (IHC) to investigate the cellular mechanisms of neurulation within Actinopterygii fish, in which so far only teleosts have been shown to undergo secondary neurulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our literature review suggests that early branching chordates likely neurulate via exclusively primary neurulation and do not have a mesenchymal tailbud. In contrast, in the Vertebrate species in which secondary neurulation has been previously documented, there is a strong positive correlation between the onset of secondary neurulation and of a mesenchymal tailbud extension. The mechanisms of neurulation have not been well characterised across the Chordates, resulting in a patchy reported distribution of secondary neurulation. MicroCT images demonstrated that tropical gar fish from the Holostei clade neurulate via secondary-like mechanisms along most of their axis, whilst Senegal bichir (Cladistia clade) and sterlet sturgeon (Chondrostei clade) exhibit primary neurulation in anterior regions and have an undifferentiated tailbud at the posterior end of the embryo. Higher resolution IHC data demonstrated that the sterlet embryo neural tube forms via primary mechanisms until a neuroenteric canal, whilst proliferative, Sox2-positive cells in the tailbud intercalate into the extending neural tube via secondary mechanisms of neurulation, without &lt;i&gt;de novo&lt;/i&gt; lumen formation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Together, our findings suggest that the cellular mechanisms of secondary neurulation likely evolved in the Vertebrata subphylum to enable cells from an extending mesenchymal tailbud to be incorporated into an already polarised posterior spinal cord. However, it remains unclear why different cellular mechanisms of secondary neurulation exist between species (e.g. &lt;i&gt;de novo&lt;/i&gt; polarisation and cell interdigitation vs. only cell interdigitation) and why some species undergo secondary neurulation along the majority of their axis whilst in others it is limited to the tailbud. We suggest that varying geometrical constraints","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1870085"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165236","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":"A bittersweet symphony: soluble mediator networks orchestrate melanoma plasticity and therapeutic adaptation.","authors":"Carmine Lauretta, Carmela Sorrentino, Emilia Sabbatino, Viviana Tutino, Deborah Simão de Souza, Antimo Migliaccio, Gabriella Castoria, Pia Giovannelli, Marzia Di Donato","doi":"10.3389/fcell.2026.1905416","DOIUrl":"https://doi.org/10.3389/fcell.2026.1905416","url":null,"abstract":"<p><p>Melanoma progression and therapeutic resistance are increasingly recognized as emergent properties of the dynamic interactions between tumor cells and their surrounding tumor microenvironment (TME). A central feature of this adaptability is melanoma cell plasticity, through which tumor cells reversibly transition between distinct transcriptional and functional states in response to microenvironmental and therapeutic pressures. Recent advances in single-cell RNA sequencing and spatial transcriptomics have revealed that these interactions are spatially organized, with distinct cellular compositions and signaling programs forming specialized microenvironmental niches. However, the mechanisms that coordinate these spatially and functionally heterogeneous states remain incompletely integrated. In this review, we propose that soluble mediator networks, including cytokines, chemokines, growth factors, metabolites, extracellular vesicle-associated signals, and stress-related mediators, provide a functional layer that links the different compartments of the melanoma TME. We organize this network into interconnected immunoregulatory, vascular and lymphatic, mechanotransductive/ECM, and metabolic/redox axes, and examine how their reciprocal interactions influence melanoma cell identity, immune surveillance, vascular function, tissue architecture, and metabolic adaptation. Particular attention is given to the context-dependent activity of soluble mediators, whose effects vary according to their cellular source, spatial distribution, disease stage, and therapeutic pressure. We further discuss how these signals converge within localized microenvironmental niches to promote melanoma plasticity, immune escape, metastatic dissemination, and therapeutic resistance. Emerging mechanisms, including metabolic rewiring, lactate signaling, oxidative stress, and transmissible endoplasmic reticulum stress, illustrate how adaptive information can propagate between the different compartments. Overall, we propose that therapeutic resistance should not be viewed solely as the consequence of tumor-intrinsic alterations or isolated resistance pathways, but as an emergent property of a continuously rewired tumor ecosystem. This perspective suggests that effective therapeutic strategies may require disruption of the adaptive communication networks that sustain resistant tumor states, rather than targeting individual molecular pathways in isolation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1905416"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166174","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":"Multimodal profiling uncovers an aging-associated ETS1-MYO1B vascular niche responsive to ipragliflozin.","authors":"Mingzhu Jin, Yue Zhang, Haien Wu, Bo You, Ling Li, Xiuping Han, Yan Wu","doi":"10.3389/fcell.2026.1968248","DOIUrl":"https://doi.org/10.3389/fcell.2026.1968248","url":null,"abstract":"<p><strong>Background: </strong>Tissue aging involves complex changes in vascular, immune, and stromal compartments that collectively reshape the local tissue ecosystem and may contribute to age-related diseases, including cancer, fibrotic diseases, and cardiovascular disease. However, it remains unclear whether reproducible, cell-specific vascular niche states emerge during aging and whether these states can be therapeutically targeted.</p><p><strong>Methods: </strong>A machine-learning single-cell age-clock model was constructed using three published human skin single-cell transcriptomic datasets and validated against chronological age. Vascular subpopulations were resolved by NMF clustering and diffusion pseudotime analysis. These findings were further validated in 15 human skin samples using H&E-based digital image analysis and immunohistochemistry. An inflammatory HMEC-1 model was used for RT-qPCR, flow cytometry, SA-β-gal staining, siRNA knockdown, and ChIP-qPCR. Structure-based virtual screening of an FDA drug library, molecular dynamics simulation, and biolayer interferometry were used to identify and validate ETS1-targeting compounds. Efficacy was assessed <i>in vivo</i> in a D-galactose-induced aging model treated with oral ipragliflozin.</p><p><strong>Results: </strong>Predicted age correlated with chronological age, with vascular endothelial cells, lymphatic endothelial cells, and pericytes carrying the strongest aging signals. Aged skin showed a higher low-hematoxylin-area burden, reduced boundary-complexity variation, and reduced vascular-area heterogeneity. An aging-associated pericyte subcluster marked by MYO1B was identified, together with a continuous endothelial-to-pericyte transition (EndoPT). TGF-β1/IL-1β stimulation induced MYO1B- and PDGFRB-positive pericyte-like transition and senescence in HMEC-1 cells. ETS1 bound the MYO1B promoter and was associated with aging status. Ipragliflozin bound the transcription-regulatory region of ETS1, suppressed the ETS1-MYO1B axis, reduced EndoPT and senescence <i>in vitro</i>, and restored epidermal thickness while reducing MYO1B, PDGFRB, and PAI-1 in aged rat skin.</p><p><strong>Conclusion: </strong>Multimodal profiling identifies an aging-associated ETS1-MYO1B vascular niche characterized by heightened inflammation, endothelial-to-pericyte plasticity, and cellular senescence, and demonstrates that this niche can be therapeutically targeted with ipragliflozin. As these processes also contribute to the microenvironmental remodeling observed in cancer and other age-related diseases, this niche may provide broader insight into how vascular and stromal alterations shape tissue aging and disease susceptibility.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1968248"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166332","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":"Transcription-dependent polyadenylation signal activity contributes to transcriptomic regulation during Forskolin-induced BeWo cell syncytialization.","authors":"Juan Liu, Guolin Ye, Xin Liu, Haiming Jing, Shan Gao, Zhongyuan Deng, Junyu Ning","doi":"10.3389/fcell.2026.1958080","DOIUrl":"https://doi.org/10.3389/fcell.2026.1958080","url":null,"abstract":"<p><p>Polyadenylation, a core transcriptional step governed by polyadenylation signals (PAS), functionally interacts with transcription. Nevertheless, how PAS sequences respond to variable transcriptional output remains poorly characterized. Here, we precisely modulated cellular transcription levels by integrating SV40 promoter truncation with a Tet-On dual-luciferase reporter system. Diminished polyadenylation efficiency accompanies lowered promoter activity, and graded transcription assays revealed a tiered PAS processing model: canonical and suboptimal PASs maintain stable 3'-end processing at high transcription levels, whereas non-canonical PASs display compromised processing efficiency with rising transcription. During forskolin(FSK)-induced BeWo cell syncytialization, endogenous trophoblast fusion genes carrying potent canonical PASs were selectively mobilized upon transcriptional activation to enrich differentiation transcripts and sustain orderly syncytiotrophoblast maturation. Together, these findings reveal a hierarchical transcription-polyadenylation axis that associate with placental trophoblast syncytialization. They fill key gaps in mRNA processing and provide a foundation for studying the transcriptional regulatory mechanisms underlying trophoblast differentiation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1958080"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166367","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":"Therapeutic potential of maggot-derived bioactive peptides in modulating inflammatory responses in mice model of inflammatory bowel disease.","authors":"Lina Zhou, Yan Chen, Mingfeng Liu, Mei Wu, Haojie Deng, Zhiwei Miao, Xiaoyu Wang, Chunyu Zhang, Ke Hua, Chanchan Guan, Jingjing Cao","doi":"10.3389/fcell.2026.1976594","DOIUrl":"https://doi.org/10.3389/fcell.2026.1976594","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease (IBD) is characterized by chronic inflammation and disruption of intestinal integrity. This study investigates the therapeutic effects of Maggot-Derived Bioactive Peptides (BPM) in alleviating IBD symptoms and restoring intestinal function.</p><p><strong>Methods: </strong>Using an IBD model, we assessed the impact of BPM on inflammatory responses, intestinal morphology, goblet cell density, and tight junction protein expression. Serum levels of inflammatory and oxidative stress markers were also measured to evaluate systemic effects.</p><p><strong>Results: </strong>BPM significantly alleviated inflammatory responses in IBD, as evidenced by decreased levels of pro-inflammatory cytokines, including TNF-α. Treatment with BPM enhanced intestinal morphology and increased goblet cell density, promoting mucosal barrier function. Furthermore, BPM regulated p-p65 and TNF-α pathways, effectively mitigating inflammation. Serum analysis revealed that BPM modulated the expression of inflammatory and oxidative stress markers. Importantly, BPM preserved intestinal wall integrity by upregulating tight junction proteins ZO-1, occludin, and claudin-1.</p><p><strong>Discussion: </strong>Our findings suggest that BPM is a promising therapeutic agent for IBD, exerting anti-inflammatory effects, enhancing intestinal morphology, and preserving epithelial integrity through multiple mechanisms. Further investigations are warranted to explore BPM's potential as a standard treatment option for IBD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1976594"},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167916","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}