Frontiers in Cell and Developmental Biology最新文献

{"title":"The vascular endothelium as decision maker in lung injury.","authors":"Diana Klein","doi":"10.3389/fcell.2025.1564627","DOIUrl":"https://doi.org/10.3389/fcell.2025.1564627","url":null,"abstract":"<p><p>The vascular endothelium is the largest organ in the human body, capable of performing a wide range of cellular signaling and synthetic functions. It is also subjected to considerable mechanical stress due to the shear forces generated by blood flow, which amounts to approximately 10,000 L per day. The endothelial layer plays a crucial role in regulating vascular tone locally and controlling the extravasation of certain blood components. Additionally, it is integral to the coagulation process. The endothelium serves as the entry point for immune cells, which migrate from the bloodstream to surrounding tissues by passing through the endothelial layer. This underscores the importance of proper endothelial function for the health of the body's tissues and organs. When the endothelium fails to perform these functions adequately, leading to endothelial dysfunction, pathological conditions are more likely to develop. Notably, acute lung injury and its severe form, acute respiratory distress syndrome (ARDS), are often associated with endothelial dysfunction. ARDS refers to pulmonary edema with increased vascular permeability resulting from various pulmonary or systemic insults. In most cases, an exaggerated inflammatory and pro-thrombotic response to the initial insult causes disruption of the alveolar-capillary membrane and leakage of vascular fluid. This review emphasizes the central role of the vascular endothelium in acute conditions and seeks to clarify the concepts and interplay between endothelial activation, dysfunction, and damage.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1564627"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682337","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":"Wnt-dependent mechanism of the apical constriction of roof plate cells in developing mouse spinal cord.","authors":"Takuma Shinozuka, Tadashi Okubo, Noriaki Sasai, Shinji Takada","doi":"10.3389/fcell.2025.1571770","DOIUrl":"https://doi.org/10.3389/fcell.2025.1571770","url":null,"abstract":"<p><p>Apical constriction of epithelial cells usually occurs in a local portion of epithelial sheet, which results in bending of epithelial tissues. However, it is uncertain whether diffusible signal molecules, like Wnt, regulate such locally restricted events. Here, we show that Wnt ligands are required for apical constriction of Wnt1-expressing roof plate (RP) cells during development of the neural tube. Analysis of <i>Wntless</i> conditional knock-out (cKO) embryos, in which Wnt secretion from Wnt1-expressing roof plate cells is impaired, revealed that RP-derived Wnt ligands are required for phosphorylation of myosin light chain (MLC) and apical constriction of RP cells. Loss- or gain-of-function analysis of β-catenin reveals that this apical constriction is regulated in a β-catenin-dependent manner. Consistent with the timing of apical constriction, Wnt ligands accumulate on the apical side of RP cells. In embryos with Wnt1-expressing RP-specific defects in synthesis of heparan sulfate proteoglycan, apical accumulation of Wnt ligands and apical constriction are impaired. Therefore, we propose that specific accumulation of Wnt ligands on RP cells drives apical constriction of these cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1571770"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682249","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":"Editorial: Advancements in hematopoietic stem cell proliferation and self-renewal maintenance.","authors":"Pawan Kumar Raghav, Gurudutta Gangenahalli, Takahiko Hara","doi":"10.3389/fcell.2025.1607145","DOIUrl":"https://doi.org/10.3389/fcell.2025.1607145","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1607145"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682335","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":"Water temperature modulates multidimensional plastic responses to water flow during the ontogeny of a neotropical fish (<i>Astyanax lacustris</i>, characiformes).","authors":"Leandro Lofeu, Bianca Bonini-Campos, Tiana Kohlsdorf","doi":"10.3389/fcell.2025.1531162","DOIUrl":"https://doi.org/10.3389/fcell.2025.1531162","url":null,"abstract":"<p><strong>Introduction: </strong>Plastic phenotypes result from multidimensional developmental systems responding to distinct yet simultaneous environmental signals, which may differently affect the magnitude and directions of plastic responses.Concomitant environmental signals during development may result in dominant, synergistic, or even antagonistic phenotypic effects, so that a given condition may amplify or minimize plastic responses to other environmental stimuli. Knowledge on how external information shapes complex plastic phenotypes is essential to predict potential evolutionary trajectories driven by developmental plasticity.</p><p><strong>Methods: </strong>Here, we manipulate water temperature to evaluate its effects on the well-described phenotypic accommodation of fish growth in the presence of water flow, using the neotropical species <i>Astyanax lacustris</i>. We include larval and juvenile ontogenetic stages to examine the interaction between these two environmental signals in plastic responses related to body size and shape, skeleton ossification and gene expression, using <i>bmp4</i> as a proxy for ossification pathways.</p><p><strong>Results and discussion: </strong>Our results demonstrate that water temperature plays a crucial role determining the expression of plastic variation at all dimensions, and effects of water flow were restricted to specific thermal regimes. Combination of high temperature and water flow has a major effect on body shape and unveils unique phenotypic patterns, supporting the prediction that high temperatures can amplify plastic responses to external signals. Specifically, fish raised in the presence of water flow at warmer environments grew faster and ossified earlier, and this condition increased <i>bmp4</i> expression levels especially at later developmental stages. Such plastic phenotypes likely involve a functional relationship with swimming performance in running-water environments. Our findings highlight the importance of studying developmental plasticity in complex environments using a multidimensional approach, especially considering increments in water temperatures due to accelerated climate changes that likely impact the fish developmental potential to mitigate environmental changes through plastic responses.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1531162"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682338","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":"Evaluating multiple large language models on orbital diseases.","authors":"Qi-Chen Yang, Yan-Mei Zeng, Hong Wei, Cheng Chen, Qian Ling, Xiao-Yu Wang, Xu Chen, Yi Shao","doi":"10.3389/fcell.2025.1574378","DOIUrl":"https://doi.org/10.3389/fcell.2025.1574378","url":null,"abstract":"<p><p>The avoidance of mistakes by humans is achieved through continuous learning, error correction, and experience accumulation. This process is known to be both time-consuming and laborious, often involving numerous detours. In order to assist humans in their learning endeavors, ChatGPT (Generative Pre-trained Transformer) has been developed as a collection of large language models (LLMs) capable of generating responses that resemble human-like answers to a wide range of problems. In this study, we sought to assess the potential of LLMs as assistants in addressing queries related to orbital diseases. To accomplish this, we gathered a dataset consisting of 100 orbital questions, along with their corresponding answers, sourced from examinations administered to ophthalmologist residents and medical students. Five language models (LLMs) were utilized for testing and comparison purposes, namely, GPT-4, GPT-3.5, PaLM2, Claude 2, and SenseNova. Subsequently, the LLM exhibiting the most exemplary performance was selected for comparison against ophthalmologists and medical students. Notably, GPT-4 and PaLM2 demonstrated a superior average correlation when compared to the other LLMs. Furthermore, GPT-4 exhibited a broader spectrum of accurate responses and attained the highest average score among all the LLMs. Additionally, GPT-4 demonstrated the highest level of confidence during the test. The performance of GPT-4 surpassed that of medical students, albeit falling short of that exhibited by ophthalmologists. In contrast, the findings of the study indicate that GPT-4 exhibited superior performance within the orbital domain of ophthalmology. Given further refinement through training, LLMs possess considerable potential to be utilized as comprehensive instruments alongside medical students and ophthalmologists.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1574378"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682336","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":"VE-PTP controls a fluid shear stress set point that governs cell morphological responses through Tie-2.","authors":"Keisuke Shirakura, Mana Ghanbarpour Houshangi, Kevin G Peters, Dietmar Vestweber","doi":"10.3389/fcell.2025.1603517","DOIUrl":"https://doi.org/10.3389/fcell.2025.1603517","url":null,"abstract":"<p><p>Blood flow differs between arteries and veins, hence endothelial cells in these vessels are exposed to different magnitudes of shear stress. Deviation from physiological blood flow triggers vascular remodeling, with increased or decreased flow leading to outward or inward remodeling, to adjust lumen diameter and thereby re-establish physiological shear stress. Based on this, it is assumed that endothelial cells in different vessels differ in their sensitivity to different shear stress levels. Expression levels of VEGFR3 were previously demonstrated to determine the threshold or set point for endothelial cell type specific shear stress sensitivity. Here we show, that the receptor type tyrosine phosphatase VE-PTP and the tyrosine kinase receptor Tie-2 represent another, new signaling system, that determines sensitivity and cellular responsiveness to different shear stress magnitudes or flow set points. We found that increased shear stress levels cause increased levels of VE-PTP endocytosis, which trigger, a similarly graded increase of Tie-2 activity, stimulation of FOXO1 nuclear exclusion and activation of autophagy. The VE-PTP/Tie-2 signaling mechanism controls cell alignment and elongation dependent on the magnitude of shear stress. In addition, VE-PTP/Tie-2 controls shear stress-induced cellular morphological changes independent of VEGFR2. Thus, VE-PTP/Tie-2 is a novel signaling mechanism which determines shear stress sensitivity and morphological responses of endothelial cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1603517"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674346","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":"Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer.","authors":"Helena Reyes-Gopar, Keila Adonai Pérez-Fuentes, Matthew L Bendall, Enrique Hernández-Lemus","doi":"10.3389/fcell.2025.1597245","DOIUrl":"10.3389/fcell.2025.1597245","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) accounts for twelve percent of all breast cancer cases, with a survival rate around ten percent lower than ER+/PR+ positive breast cancers. There are limited therapeutic options as these tumors do not respond to hormonal therapy or HER2-targeted treatments. We hypothesized that new insights into pathogenic mechanisms in TNBC can be obtained from studying epigenetic alterations through Hi-C (genome-wide chromosome conformation capture) data analysis.</p><p><strong>Methods: </strong>We developed a computational strategy that captured key properties of chromatin conformation while incorporating statistical measures of interaction significance. This model addresses limitations in Hi-C data analysis without relying on predefined features like TADs and compartments. We applied this model to Hi-C and RNA-seq data from TNBC patients, representing the data as multilayer networks to identify genome-wide properties of the TNBC 3D genome.</p><p><strong>Results: </strong>Our network-based analysis revealed distinct chromatin interaction patterns in TNBC compared to healthy contralateral controls. Hi-C data can distinguish interaction patterns related to diseased phenotypes or interaction patterns with potential to exert regulatory effects instead of incidental contacts, but some apparently random interactions may also support important genome regulatory activities.</p><p><strong>Discussion: </strong>Our findings demonstrate that network-based Hi-C analysis can capture the genome-wide complexity of chromatin interactions in TNBC. This integrative approach provides new insights into the epigenetic mechanisms underlying TNBC pathogenesis and contributes to the advancement of analysis methods for future investigations into novel therapeutic targets.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1597245"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674344","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":"Involvement of role of HMGB1-NLRP3 pathway in systemic disorders.","authors":"Lei Yang, Xue Li, Xiaoming Zhu, Futao Ge, Yuantao Wang","doi":"10.3389/fcell.2025.1600596","DOIUrl":"https://doi.org/10.3389/fcell.2025.1600596","url":null,"abstract":"<p><p>High mobility group box-1 (HMGB1) is a protein released from stressed or damaged cells that triggers immune activation and chronic inflammation. The NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) is a central component of the inflammasome, which activates caspase-1 and releases pro-inflammatory cytokines, including IL-1β and IL-18. The HMGB1/NLRP3 axis plays a critical role in regulating inflammation and immune responses, driving systemic inflammation and disease progression. Targeting this pathway offers promising therapeutic strategies for conditions such as autoimmune disorders, trauma, and chronic inflammatory diseases. In particular, inhibiting HMGB1 or NLRP3 can mitigate the exaggerated inflammatory response, reduce tissue damage, and slow disease progression. This review explores the bidirectional interactions between HMGB1 and NLRP3 and discusses current and emerging therapeutic approaches targeting this axis to modulate inflammation and improve clinical outcomes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1600596"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674345","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":"Selective blockade of acid-sensing ion channel 1a can provide substantial hippocampal neuroprotection.","authors":"Jiaai Li, Yu Cheng, Di Ma, Guangjian Li, Weixuan Zhao, Ting Jiang, Hongmei Meng","doi":"10.3389/fcell.2025.1582970","DOIUrl":"10.3389/fcell.2025.1582970","url":null,"abstract":"<p><strong>Background: </strong>Acid-sensing ion channel 1a (ASIC1a) is the only member of the ASIC family where Ca²⁺ osmosis has been reported, and it is highly expressed in neurons of the central nervous system. This study aimed to investigate whether ASIC1a is trafficked to the plasma membrane and regulated by the Rho/ROCK and PI3K signaling pathways in temporal lobe epilepsy (TLE). In addition, further research is required to determine whether selective ASIC1a blockade is a viable therapeutic strategy for TLE.</p><p><strong>Methods: </strong>The localization and expression levels of ASIC1 and mRNA levels of ASIC1a were detected when the Rho/ROCK and PI3K signaling pathways were activated and inhibited in glutamate (Glu)-induced cell. Meanwhile, we analyzed the location and expression of ASIC1 using Western blotting and immunofluorescence in brain tissue samples from TLE patients, kainic acid (KA)-treated rats, and Glu-induced primary hippocampal neurons. Currently, no specific ASIC1a antibody is available, so the ASIC1 antibody was used in this study, as in previous studies. Furthermore, we evaluated the HT22 cell survival rate, mitochondrial damage, apoptosis, and autophagy to examine whether selective blocking ASIC1a (PcTx1) could play a neuroprotective role.</p><p><strong>Results: </strong>First, the Rho/ROCK and PI3K signaling pathways affect the regulation of the expression and localization of ASIC1, especially the mRNA levels of ASIC1a in the Glu-induced HT22 cell injury model. Second, the high expression of ASIC1 in epilepsy patients was verified in all three sample types, and the phenomenon of its transport from the cytoplasm to the cell membrane/mitochondria was confirmed. Finally, although ASIC1 has a limited epileptogenic effect in the acute phase of epilepsy <i>in vivo</i>, selective blockade of ASIC1a using PcTx1 provided significant hippocampal neuroprotection and reduced mitochondrial damage, apoptosis, and cellular autophagy <i>in vitro</i>.</p><p><strong>Interpretation: </strong>This study is a systematic report concerning ASIC1a in temporal lobe epilepsy, including <i>in vivo</i> and <i>in vitro</i> experiments addressing both the acute and chronic phases. It provides foundational research for proposing ASIC1a as a new target for epilepsy treatment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1582970"},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658819","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":"How the chromatin landscape influences nuclear morphology.","authors":"Sourabh Sengupta, Haritha Prabha, Daniel L Levy","doi":"10.3389/fcell.2025.1634252","DOIUrl":"10.3389/fcell.2025.1634252","url":null,"abstract":"<p><p>Nuclear morphology is a defining cellular feature, differing based on cell type, tissue type, and species. In healthy cells, nuclear morphology is generally tightly regulated and maintained; however, dynamic changes in nuclear morphology are observed under certain conditions, for instance in early embryos and in some immune cells. Deviations in normal nuclear morphology are linked to numerous diseases, including most cancers and premature aging syndromes. Many regulators of nuclear morphology have been identified, encompassing both intranuclear, cytoplasmic, and extracellular factors. Of note, recent studies have converged on chromatin and chromatin-associated proteins as key determinants of nuclear morphology and dynamics. In this review we discuss how the chromatin landscape regulates nuclear morphology in both normal and diseased cellular states. Additionally, we highlight emerging technologies that promise to bridge critical gaps in our understanding of nuclear morphology, including new approaches to probe nuclear structure and the use of synthetic cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1634252"},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658817","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}