Frontiers in Cell and Developmental Biology最新文献

{"title":"Extracellular vesicles in the immune regulation of hematological malignancies: mechanisms, prognostic significance, and therapeutic opportunities.","authors":"Tuya Wang, Jing Fu, Ye Huang, Jing Xu, Chun Fu","doi":"10.3389/fcell.2026.1941887","DOIUrl":"https://doi.org/10.3389/fcell.2026.1941887","url":null,"abstract":"<p><p>The progressive cross-talk between tumor cells and the immune microenvironment, which is required for tumor growth, progression, and dissemination, has been well documented in solid cancers and is increasingly recognized in hematological malignancies. Extracellular vesicles (EVs) are now emerging as essential facilitators of immune-tumor crosstalk. In hematological cancers, EVs from leukemia, lymphoma, and myeloma cells carry oncogenic proteins, lipids, cytokines, and non-coding RNAs that reprogram immune cells and establish tumor-promoting immune states, in which tumor cells are protected from immune elimination and therapy-induced cell death. Evidence shows that tumor-derived EVs impair antitumor immunity, in part, by promoting macrophage M2 polarization, myeloid-derived suppressor cell (MDSC) expansion, dendritic cell maturation, T-cell exhaustion, and NK-cell cytotoxicity. Tumor cell-derived EV cargo, such as PD-L1, TGF-β, IL-10, and tumor-encoded miRNAs, creates highly immunosuppressive niches that promote disease progression and are associated with a dismal prognosis. On the other hand, immune-cell-derived or engineered EVs can activate CD4⁺ and CD8⁺ T cells, augment NK-cell killing, and serve as highly potent vehicles for antigen delivery or immune checkpoint modulation. By modifying the EV cargo, blocking EV uptake, or using EVs as vaccines or targeted delivery vehicles, it is now possible to restore antitumor immunity and reverse immunotherapy resistance. This review will provide an update on the current understanding of EVs in the regulation of hematological cancers, from mechanistic, translational, and therapeutic perspectives. We will also discuss the potential of using EVs as biomarkers and as next-generation immunotherapeutic agents.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1941887"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180433","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":"DHA elongates the neuronal primary cilium through GPR40-mediated signaling.","authors":"Kento Karita, Mariko Yokota, Yuzuki Toyonaga, Riko Takase, Naoyuki Inagaki, Maki K Yamada, Ikuko Yao, Manami Toriyama, Michinori Toriyama","doi":"10.3389/fcell.2026.1910684","DOIUrl":"https://doi.org/10.3389/fcell.2026.1910684","url":null,"abstract":"<p><strong>Introduction: </strong>Docosahexaenoic acid (DHA), the predominant n-3 polyunsaturated fatty acid (PUFA) in the brain, promotes neuronal differentiation, neurite outgrowth, and synapse formation. However, the subcellular mechanisms underlying these effects remain unclear. The primary cilium functions as a signaling antenna, with its length influencing signaling capacity; however, the physiological factors regulating cilium length in neurons are largely unknown. This study investigated whether DHA promotes primary cilium elongation in neurons and examined the underlying signaling pathways.</p><p><strong>Methods: </strong>Primary cilium length was measured in cultured mouse hippocampal neurons immunostained for adenylyl cyclase 3, and in the embryonic cerebral cortex immunostained for ARL13B after maternal dietary or pharmacological manipulation of DHA and GPR40 signaling. The pathway was dissected using selective receptor agonists and antagonists, RNAi-mediated knockdown, live-cell calcium imaging, RT-qPCR, Western blotting, and ELISA.</p><p><strong>Results: </strong>DHA increased cilium length in a concentration- and time-dependent manner, with the increase observable within 24 h and sustained thereafter in cultured neurons. Consistently, maternal dietary n-3 fatty acid intake modulated cilium length in the developing fetal brain, with high n-3 diet leading to elongation and low n-3 diet resulting in shortening. DHA-induced ciliary elongation was mediated by GPR40, as this effect was abolished by a selective GPR40 antagonist <i>in vitro</i> and recapitulated by selective GPR40 agonists both <i>in vitro</i> and <i>in vivo</i>. DHA rapidly increased intracellular Ca²⁺ levels, and pharmacological inhibition of calcineurin-NFAT signaling suppressed DHA-induced ciliary elongation. DHA selectively induced cyclooxygenase-2 (COX-2) at both the mRNA and protein levels, and COX-2 activity was essential for elongation. Finally, DHA elevated prostaglandin E2 (PGE2) levels, and pharmacological blockade of EP4 suppressed DHA-induced ciliary elongation, indicating that PGE2-EP4 signaling contributes to this process.</p><p><strong>Discussion: </strong>By identifying the regulation of cilium length as a previously unrecognized action of DHA, this study uncovers a subcellular mechanism by which dietary n-3 fatty acids may influence neuronal primary cilia.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1910684"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180478","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":"TRPV4-linked oxidative-lysosomal stress in myocardial ischemia/reperfusion: disease-matched transcriptomics and functional analysis in OGD/R cardiomyoblasts.","authors":"Jie Yang, Jincheng Li, Guanyao Li, Heyu Zhong, Hang Yang, Kai Zhong, Fan Wang, Zhou Huang, Dongling Huang, Wanxia Wei, Xueling Lu, Guodong Pang, Yuqinlin Chen, Yiling Zhai, Wei Wang","doi":"10.3389/fcell.2026.1945533","DOIUrl":"https://doi.org/10.3389/fcell.2026.1945533","url":null,"abstract":"<p><strong>Background: </strong>Myocardial ischemia/reperfusion (MI/R) injury involves oxidative stress, lysosomal dysfunction, and altered autophagy. TRPV4 may link Ca²⁺ dysregulation to these processes, but its role in lysosomal membrane permeabilization (LMP) and autophagic impairment remains unclear.</p><p><strong>Methods: </strong>Three disease-matched mouse-heart GEO cohorts (GSE281940, GSE130217, and GSE160516) were analyzed using limma-based differential expression, prespecified oxidative, lysosomal, and autophagy-related gene sets, cross-cohort comparisons, and within-cohort correlations. H9C2 cardiomyoblasts subjected to OGD/R were used to examine intracellular Ca²⁺, ROS, LMP, autophagy-related changes, inflammatory cytokine release, and cell injury after pharmacological modulation of TRPV4 and ROS.</p><p><strong>Results: </strong>All three cohorts showed clear MI/R-associated transcriptional changes. Hmox1 was consistently increased across all five prespecified contrasts, whereas <i>Trpv4</i> showed modest, time-dependent changes without reaching FDR-adjusted significance. <i>Trpv4</i> was positively correlated with <i>Map1lc3b</i> in all three cohorts (Spearman ρ = 0.73-0.83, nominal P < 0.05), while associations with oxidative and lysosomal genes were more variable. In H9C2 cardiomyoblasts, OGD/R increased TRPV4 mRNA expression, intracellular Ca²⁺, and ROS levels. TRPV4 inhibition reduced ROS accumulation, attenuated LMP-related changes, and decreased LC3B and p62 accumulation, whereas TRPV4 activation produced the opposite effects. NAC attenuated TRPV4 activation-induced ROS and lysosomal injury, while t-BHP partially reversed the effects of TRPV4 inhibition. OGD/R also increased IL-1β, IL-6, and TNF-α release, which was reduced by TRPV4 inhibition.</p><p><strong>Conclusion: </strong>The transcriptomic data indicate a context-dependent TRPV4 response within a conserved MI/R stress background. The H9C2 cardiomyoblasts experiments support the involvement of the TRPV4-ROS-LMP pathway in lysosomal injury, impaired autophagic degradation, inflammatory responses, and OGD/R-induced cardiomyoblast injury.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1945533"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180549","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":"Understanding the involvement of HtrA4 during syncytiotrophoblast differentiation.","authors":"Bothidah Thach, Yao Wang, Chaitali Dekiwadia, Guiying Nie","doi":"10.3389/fcell.2026.1926149","DOIUrl":"https://doi.org/10.3389/fcell.2026.1926149","url":null,"abstract":"<p><p>The syncytiotrophoblast (STB), the outermost layer of the human placenta, is vital to pregnancy health as it functions as the direct maternal-fetal interface. Being terminally differentiated and multinucleated, STB cannot divide but is formed/sustained by fusion of cytotrophoblasts throughout pregnancy. HtrA4, produced only in placentas of humans and high-order primates, is obligatory for syncytialization, including differentiation of trophoblast stem cells (TSCs) into STB as HtrA4 knockdown (KD) blocks the process; however, how HtrA4 mediates the process remains unknown. The current study aimed to understand how HtrA4 is involved in STB differentiation, by analyzing HtrA4-KD TSCs using mRNA transcriptomics and scanning electron microscopy (SEM). We first investigated how control and HtrA4-KD TSCs, respectively, altered protein-coding gene expressions globally upon stimulation for STB differentiation, then compared the significantly differentially expressed genes (DEGs) to identify the deficiencies of HtrA4-KD cells. Among the DEGs associated with STB differentiation of controls, 25% of them also occurred in HtrA4-KD cells, implying these were HtrA4-independent; in contrast, the remaining 75% DEGs were severely attenuated or completely blocked in HtrA4-KD cells, signifying these were HtrA4-modulated or HtrA4-dependent. Analysis of biological processes, molecular functions, and cellular pathways associated with these distinctive DEGs suggested that early STB differentiation events, such as ceasing cell division and initiating autophagy, were un-influenced by HtrA4. However, many subsequent processes of STB differentiation were partially or fully influenced by HtrA4, some of which included hormone activity, cell surface and extracellular matrix remodeling, adjustments in cell-cell signaling, and restructuring of various components of the cytoplasm/cytoskeleton. Moreover, our data suggested that pathways related to nervous system development were suppressed during STB differentiation, and this was influenced by HtrA4. Furthermore, it was indicated that altering protein binding was a major juncture of HtrA4 influence, and mitigating oxidative stress during STB differentiation might be tightly coupled with HtrA4. By SEM examination of the morphological changes along the time course of STB differentiation, we further visually demonstrated that HtrA4-KD cells commenced the differentiation process, but were blocked from progressing into multinucleated STB. Collectively, these findings provide important new insights into the pivotal role of HtrA4 in STB differentiation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1926149"},"PeriodicalIF":5.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180572","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":"Retinal organoid-based evaluation of icariin-loaded extracellular vesicles for hypoxia-induced retinal injury via mitochondrial modulation.","authors":"Mira Park, Hyeoun Ji Kim, Yoon-Ha Go, Hey Jin Lee, Young Il Yang, Dong Hyuck Bae, Jong Man Yoo, Helen Lew","doi":"10.3389/fcell.2026.1891491","DOIUrl":"https://doi.org/10.3389/fcell.2026.1891491","url":null,"abstract":"<p><strong>Background: </strong>Hypoxic injury is a critical pathological factor in various retinal degenerative diseases, leading to mitochondrial dysfunction and irreversible loss of retinal neurons. This study investigated the neuroprotective potential of Icariin-loaded extracellular vesicles (EV_ICA) using both R28 retinal progenitor cells and human embryonic stem cell (hESC)-derived retinal organoids.</p><p><strong>Methods: </strong>EV_ICA were isolated and characterized by morphology, EV marker expression, and zeta potential analysis. A CoCl₂-induced hypoxic injury model was established in R28 cells and hESC-derived retinal organoids to evaluate the therapeutic effects of EV_ICA. Gene and protein expression analyses, bulk RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), mitochondrial ROS measurements, and intracellular ATP assays were performed to assess neuroprotective efficacy and mitochondrial function.</p><p><strong>Results: </strong>EV_ICA exhibited typical spherical morphology, expressed standard EV markers, and showed a shift toward a less negative zeta potential compared to Naïve EV. In hypoxia-injured retinal models, EV_ICA significantly restored the expression of key retinal and neuroprotective markers, including Syntaxin12, NeuN, Vegf, Rbpms, Brn-3a, and Bdnf, while suppressing Hif-1α accumulation. Transcriptomic and GSEA analyses revealed that EV_ICA reactivated biological pathways associated with phototransduction, visual perception, and retinal development that were impaired under hypoxic conditions. Furthermore, EV_ICA improved mitochondrial homeostasis by up-regulating mitochondrial-related genes, reducing mitochondrial ROS accumulation, and recovering intracellular ATP production.</p><p><strong>Conclusion: </strong>These findings demonstrate that EV_ICA exerts neuroprotective effects by preserving mitochondrial quality control and restoring functional retinal gene programs under hypoxic stress. EV_ICA may therefore serve as a promising therapeutic candidate for hypoxia-related retinal degeneration and provide potential applications for cell-free regenerative medicine.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1891491"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180591","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":"Mitochondrial protein import stress in Parkinson's disease: the TOM/TIM-PINK1/Parkin-DELE1/HRI axis linking mitochondrial proteostasis to neuronal death.","authors":"Bo Pang, Xin Li, Yunlong Sun, Lin Ding","doi":"10.3389/fcell.2026.1935788","DOIUrl":"10.3389/fcell.2026.1935788","url":null,"abstract":"<p><p>Mitochondrial dysfunction is a hallmark of Parkinson's disease (PD), but how impaired mitochondrial homeostasis drives the selective death of dopaminergic neurons is still poorly understood. At the center of this problem lies the mitochondrial protein import machinery-the TOM and TIM23 translocases-which doubles as a stress-sensing hub that coordinates two distinct quality control pathways. When import is compromised, the kinase PINK1 accumulates on the mitochondrial surface, recruits Parkin to ubiquitinate outer membrane proteins, and triggers mitophagy. Meanwhile, the stress sensor DELE1 is cleaved and released to the cytosol, where it activates the HRI kinase to phosphorylate eIF2α and engage the integrated stress response (ISR). These two pathways are not independent. Recent work shows they engage in antagonistic crosstalk: the DELE1-HRI-ISR axis suppresses PINK1/Parkin-dependent mitophagy by preserving mitochondrial import efficiency, acting as a molecular brake on organelle clearance. The balance between these pathways is governed by the SIFI E3 ubiquitin ligase complex, which targets both DELE1 and HRI for degradation. Disruption of SIFI causes progressive neurodegeneration in humans. Here we synthesize the structural, biochemical, and genetic evidence that defines the TOM/TIM-PINK1/Parkin-DELE1/HRI signaling axis, examine how its dysregulation contributes to dopaminergic neuron vulnerability, and evaluate therapeutic strategies targeting mitochondrial import stress in PD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1935788"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165818","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":"Immune-related molecular links between asthma and Alzheimer's disease identified by multi-omics, machine learning and single-cell analysis.","authors":"Li-Jie Yang, Ni-Shan Deng, Miao-Juan Zhu, Xiu Shi, Jiong Yang, Han-Xiang Nie","doi":"10.3389/fcell.2026.1907664","DOIUrl":"10.3389/fcell.2026.1907664","url":null,"abstract":"<p><strong>Objective: </strong>Epidemiological evidence suggests that asthma increases the risk of Alzheimer's disease (AD), yet their shared immune-related molecular mechanisms remain unclear. This study aimed to identify immune-associated molecular links between the two diseases.</p><p><strong>Methods: </strong>Gene expression datasets from GEO were analyzed to identify differentially expressed genes (DEGs) and enriched pathways. WGCNA was used to detect immune-related modules, and machine learning algorithms were applied to refine candidate biomarkers. Mendelian randomization (MR) and experimental validation were conducted to investigate genetic associations and expression correlations. A logistic regression model and nomogram were constructed. Immune characteristics were further explored using GSEA, immune-cell signature analysis, and single-cell RNA sequencing (scRNA-seq).</p><p><strong>Results: </strong>CD163 and CHST6 were identified as cross-disease candidate genes. MR analyses showed nominal genetic associations of CD163 expression and plasma protein levels with asthma- and AD-related phenotypes, although these associations did not remain significant after FDR correction. CD163 and CHST6 also showed increased expression in independent asthma and AD mouse models. The combined diagnostic model showed good discrimination (AUC >0.87). Immune-cell signature analysis revealed tissue-dependent associations between the candidate genes and immune-related signatures. scRNA-seq revealed cell-type-specific expression patterns, with CD163 predominantly localized to myeloid-lineage populations, including microglia in AD and monocytes in severe asthma, whereas CHST6 showed context-dependent localization across glial and airway epithelial populations.</p><p><strong>Conclusion: </strong>CD163 and CHST6 represent potential cross-disease molecular candidates associated with asthma and AD. CD163 may reflect a systemic immune-associated signal, whereas CHST6 may reflect tissue- and context-dependent cellular changes. These findings provide a preliminary framework for further investigation of asthma-AD comorbidity and require validation in prospective and functional studies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1907664"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166680","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":"TMEM39A acts as a novel profibrotic factor to activate hepatic stellate cells partially via the cell adhesion molecule signaling axis.","authors":"Meng Kong, Lihong Zhang, Yuexia Bai, Jinhua Jia, Chuanyang Liu, Wei Liu, Shuai Chen, Shisong Zhang","doi":"10.3389/fcell.2026.1926987","DOIUrl":"https://doi.org/10.3389/fcell.2026.1926987","url":null,"abstract":"<p><strong>Objective: </strong>Hepatic stellate cell (HSC) transdifferentiation into myofibroblasts is a pivotal event in liver fibrosis, yet the underlying regulatory network remains elusive. This study explores the role of TMEM39A in HSC activation and its pro-fibrotic effects via the cell adhesion molecule (CAM) signaling axis.</p><p><strong>Methods: </strong>An <i>in vitro</i> HSC activation model was established using TGF-β1-stimulated LX-2 cells, combined with TMEM39A knockdown and overexpression. Cell viability, migration, and apoptosis were assessed by CCK-8, wound healing, Transwell, and flow cytometry. Fibrotic marker expression was measured at both mRNA and protein levels. RNA sequencing and bioinformatics identified the CAM pathway as a candidate downstream effector, and its pharmacological inhibitor (Alicaforsen, an ICAM-1 antagonist) was used for validation.</p><p><strong>Results: </strong>TMEM39A expression correlated positively with HSC activation. Overexpression of TMEM39A promoted LX-2 viability, migration, and upregulation of fibrotic markers (α-SMA, COL1A1) while suppressing apoptosis, whereas knockdown reversed these effects. Mechanistically, TMEM39A activated the CAM axis with specific ICAM-1 elevation. Alicaforsen treatment partially inhibited the activation of HSCs and the expression of fibrosis markers induced by TMEM39A.</p><p><strong>Conclusion: </strong>TMEM39A functions as a novel pro-fibrotic facilitator that promotes HSC activation at least partially through the CAM/ICAM-1 signaling axis. Our findings provide mechanistic insights into liver fibrosis and suggest TMEM39A and its downstream effectors as potential candidates for further therapeutic exploration, pending rigorous <i>in vivo</i> and clinical validation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1926987"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180525","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 mechanical niche in gastric precancer: extracellular matrix remodeling, mechanotransduction, and stem-cell fate.","authors":"Lanshuo Hu, Xuanchun Huang, Tai Zhang, Yeqian Wu, Liangjun Yang, Jiajie Zhu, Xudong Tang, Baoying Fei","doi":"10.3389/fcell.2026.1970363","DOIUrl":"https://doi.org/10.3389/fcell.2026.1970363","url":null,"abstract":"<p><strong>Background: </strong>The Correa cascade foregrounds infection, inflammation, and epithelial change but does not fully explain how the physical tissue environment influences progression from atrophy to metaplasia and dysplasia.</p><p><strong>Methods: </strong>We integrated human observations, gastric organoid and animal perturbation studies, advanced gastric-cancer experiments, and cross-tissue evidence using the Gastric Precancer Mechanobiology Evidence Stratification framework, which ranks evidence by proximity to causal human precancerous mechanics.</p><p><strong>Results: </strong>Direct human mechanical measurements remain sparse and methodologically heterogeneous, precluding a universal stiffening trajectory. YAP has the strongest functional support across gastric regeneration and metaplastic remodeling, integrin-adhesion signaling is convergent but mechanically under-specified, and Piezo1 evidence derives mainly from advanced cancer. Three non-exclusive models-mechanical driver, epithelial-first remodeling, and inflammation-mediated feedback-produce distinct temporal predictions.</p><p><strong>Conclusion: </strong>Gastric precancer is best understood through a mechanically extended Correa framework in which static matrix properties, dynamic loading, regional anatomy, inflammatory context, and lineage state jointly determine whether injury resolves or stabilizes abnormal epithelial states. Spatial human mechanics linked to dynamic patient-derived perturbation models are required before mechanical biomarkers or pathway-directed interventions can guide clinical care.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1970363"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180559","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":"From synapse to sheath: how OPCs couple neural activity to adaptive myelination and behavioral plasticity.","authors":"Rui Tan, Wenwen Lu, Aifen Yang, Junqing Du, Xiaofeng Xu, Xiaofeng Zhao, Mengsheng Qiu, Yu Tian","doi":"10.3389/fcell.2026.1966652","DOIUrl":"10.3389/fcell.2026.1966652","url":null,"abstract":"<p><p>Oligodendrocyte precursor cells (OPCs) are abundant progenitor cells in the central nervous system. Unlike mature oligodendrocytes, OPCs form functional synapses with neurons and respond to both glutamatergic and GABAergic signals. Glutamate activates calcium-permeable AMPA receptors on OPCs, generating local Ca²⁺ signals that regulate myelin sheath formation and stabilization. In parallel, GABAergic signaling modulates OPC proliferation and differentiation through both calcium-dependent and transcriptional mechanisms. Activity-dependent myelination driven by OPCs contributes directly to neural circuit plasticity and behavioral adaptation, including motor learning, spatial memory, fear extinction, and social experience-dependent brain development. Disruption of the OPC-synapse-myelin axis impairs remyelination and circuit function, contributing to neurological and psychiatric disorders such as multiple sclerosis, schizophrenia, and PTSD. In this review, we critically examine neuron-OPC communication across four interconnected levels: synaptic signaling, cellular fate regulation, myelin plasticity, and behavior. We highlight key limitations in the current evidence, including controversies over the functional role of OPC synapses in the adult brain, unclear mechanisms underlying myelin plasticity, and the largely correlative nature of human neuroimaging data. We argue that the field must move beyond descriptive observations toward rigorous mechanistic studies of causality, with particular attention to region- and cell-type-specific heterogeneity.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1966652"},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164444","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}