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Optimizing single cell RNA sequencing of stem cells. A streamlined workflow for enhanced sensitivity and reproducibility in hematopoietic studies. The use of human umbilical cord blood-derived hematopoietic stem and progenitor cells. 干细胞单细胞RNA测序优化。在造血研究中提高敏感性和可重复性的流线型工作流程。利用人脐带血衍生的造血干细胞和祖细胞。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1590889
Justyna Jarczak, Patrycja Kieszek, Mariusz Z Ratajczak, Magdalena Kucia
{"title":"Optimizing single cell RNA sequencing of stem cells. A streamlined workflow for enhanced sensitivity and reproducibility in hematopoietic studies. The use of human umbilical cord blood-derived hematopoietic stem and progenitor cells.","authors":"Justyna Jarczak, Patrycja Kieszek, Mariusz Z Ratajczak, Magdalena Kucia","doi":"10.3389/fcell.2025.1590889","DOIUrl":"10.3389/fcell.2025.1590889","url":null,"abstract":"<p><strong>Background: </strong>Human hematopoietic stem/progenitor cells (HSPCs) are enriched in umbilical cord blood (UCB) among cell populations that express CD34 and CD133 (PROM1) antigens. These cells can be purified further and sorted by FACS as CD34<sup>+</sup>Lin<sup>-</sup>CD45<sup>+</sup> and CD133<sup>+</sup>Lin<sup>-</sup>CD45<sup>+</sup> cells. It has been postulated that the population of CD133<sup>+</sup> HSPCs is enriched for more primitive stem cells. To address this issue at the molecular level, we performed single-cell RNA-sequencing (scRNA-seq) and analyzed the transcriptome of both cell types. We optimized the available protocols of scRNA-seq of HSPC and described our laboratory experiences with the limited number of cells obtained from human UCB.</p><p><strong>Results: </strong>Herein, we report the results of scRNA-seq analysis paying special attention to the quality parameters of single cell libraries. We also present the similarities and differences in transcriptome between these cells (CD34<sup>+</sup>Lin-CD45<sup>+</sup> and CD133<sup>+</sup>Lin-CD45<sup>+</sup> HSPCs) and their subpopulations identified and visualized as clusters using uniform manifold approximation and projection (UMAP), stressing the need for an integrated analysis of both datasets, which may be merged and treated as \"pseudobulk.\" We revealed that both populations do not differ significantly in gene expression, as evidenced by the very strong positive linear relationship between these cells (R = 0.99).</p><p><strong>Conclusion: </strong>To obtain solid results that allow to draw conclusions that would have a biological translation, all parts of the scRNA-seq experiment are crucial and must be carried out with due care: cell sorting, single cell libraries preparation, quality control, and data analysis. The idea of working with sorted material instead of the typical use of a full pellet of blood cells was right and confirmed the possibility of HSPC analysis, even with a limited number of cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1590889"},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182146","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}
引用次数: 0
Findings of preoperative patient risk factors to predict dislocation following total hip arthroplasty. 术前患者危险因素预测全髋关节置换术后脱位的发现。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1601997
Hao Li, Jinwei Xie, Xiaomin Lu, Shuai Li, Weiming Liao
{"title":"Findings of preoperative patient risk factors to predict dislocation following total hip arthroplasty.","authors":"Hao Li, Jinwei Xie, Xiaomin Lu, Shuai Li, Weiming Liao","doi":"10.3389/fcell.2025.1601997","DOIUrl":"10.3389/fcell.2025.1601997","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have identified some risk factors of dislocation after total hip arthroplasty (THA). However, there are many vital preoperative patient risk factors remaining unknown. This study aimed to investigate comprehensively patient risk factors to reduce the dislocation rate after THA.</p><p><strong>Methods: </strong>We retrospectively reviewed patients who underwent primary THA in our department between January 2016 to December 2020. All readmissions related to postoperative dislocation were recorded, and each patient who dislocated was matched with three patients who did not dislocate according to date of operation, operative time and follow-up time. Patient risk factors were initially analyzed by univariate analyses, and independent risk factors for dislocation were identified by multivariate logistic regression.</p><p><strong>Results: </strong>A total of 5,133 patients were reviewed and 76 patients were readmitted with postoperative dislocations in follow-up time (1.5%). Age (odds ratio [OR], 1.027; 95% confidence interval [CI], 1.000-1.055; P = 0.049), rheumatoid arthritis (OR, 7.976; 95% CI, 1.419-44.827; P = 0.018), low serum calcium level (OR, 0.009; 95% CI, 0.000-0.211; P = 0.003) and poor education degree (OR, 0.847; 95% CI, 0.770-0.932; P = 0.001) were determined as independent predictors associated with dislocation after THA.</p><p><strong>Conclusion: </strong>Patients with older age, rheumatoid arthritis, low serum calcium level, and poor education degree require targeted optimization of preoperative planning and should be performed by appropriate surgical techniques and hip prostheses to prevent dislocation after THA and revision surgeries.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1601997"},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181250","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}
引用次数: 0
Midline 1 associated with Fas signaling enhances murine antigen-induced arthritis. 与Fas信号相关的中线1增强小鼠抗原诱导的关节炎。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1451093
Nina Lukač, Darja Flegar, Sara Priselac, Tomislav Kelava, Alan Šućur, Maša Filipović, Dino Šisl, Martina Fadljević, Igor Radanović, Vedran Katavić, Nives Zimmermann, Danka Grčević, Nataša Kovačić
{"title":"Midline 1 associated with Fas signaling enhances murine antigen-induced arthritis.","authors":"Nina Lukač, Darja Flegar, Sara Priselac, Tomislav Kelava, Alan Šućur, Maša Filipović, Dino Šisl, Martina Fadljević, Igor Radanović, Vedran Katavić, Nives Zimmermann, Danka Grčević, Nataša Kovačić","doi":"10.3389/fcell.2025.1451093","DOIUrl":"10.3389/fcell.2025.1451093","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis is the most common immune-mediated joint disease, whose pathogenesis includes both innate and acquired immune mechanisms. Fas/Fas ligand system is considered to have a dual role in arthritis, inducing apoptotic cell death of hyperplastic synoviocytes and inflammatory cells, but also exerts proinflammatory effects. In our study, absence of Fas resulted in decreased accumulation of myeloid cells in affected joints.</p><p><strong>Methods: </strong>Proportions of synovial hematopoietic cells were assessed by flow cytometry in wild-type and <i>Fas -/-</i> mice with antigen-induced arthritis. Effects of myeloid-specific ablation of Fas on the course of antigen-induced arthritis was assessed using Fas<sup>fl</sup>/LysMCre model. Arthritis was scored visually, histologically and by micro-computerized tomography. Transcriptome of sorted CD11b<sup>+</sup>Gr-1<sup>+</sup> cells was analyzed by microarray, and effects of potential molecular driver Midline-1 (Mid-1) were analyzed <i>in vitro</i> and using <i>Mid1 -/-</i> mice.</p><p><strong>Results: </strong>Ameliorated antigen-induced arthritis in <i>Fas -/-</i> mice is characterized by the lack of synovial accumulation of myeloid CD11b<sup>+</sup>Gr-1<sup>+</sup> cells. However, myeloid-specific ablation of Fas was not sufficient to ameliorate arthritis, suggesting proinflammatory effects of Fas in multiple cell subsets in arthritis. Myeloid cells from <i>Fas -/-</i> mice downregulated limited number of genes including <i>Mid1</i>. Stimulation of bone marrow cells with low doses of soluble Fas agonist upregulated expression of <i>Mid1</i>. Inactivation of <i>Mid1</i> had a variable anti-inflammatory effects <i>in vitro</i> and partial anti-arthritic effect <i>in vivo</i>.</p><p><strong>Conclusion: </strong>Functional Fas is required for the recruitment and accumulation of innate inflammatory cells in arthritic joints. This accumulation is not driven exclusively by mediators expressed in accumulated subset. <i>Mid1</i> enhances inflammatory polarization of myeloid cells and promotes bone and cartilage degradation in arthritis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1451093"},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181756","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}
引用次数: 0
Evaluation of image analysis tools for the measurement of cellular morphology. 评价用于测量细胞形态的图像分析工具。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1572212
Matthew D Bourn, Lauren F Daly, Jim F Huggett, Julian Braybrook, Jeanne F Rivera
{"title":"Evaluation of image analysis tools for the measurement of cellular morphology.","authors":"Matthew D Bourn, Lauren F Daly, Jim F Huggett, Julian Braybrook, Jeanne F Rivera","doi":"10.3389/fcell.2025.1572212","DOIUrl":"10.3389/fcell.2025.1572212","url":null,"abstract":"<p><p>Morphological cell analysis offers a means of identification and classification of key morphological measurement parameters linked to cell bioactivity and cell health and, as such, it is of great interest to academic and industrial research sectors. Widespread adoption of this approach has yet to occur, partially due to the lack of alignment in analysis methodologies and output metrics, limiting data comparability. Work within the cell metrology and wider multidisciplinary community aims to reduce data variability through the improved alignment of image acquisition and analysis methodologies. Furthermore, to improve data comparability, research has also focused on the identification of a minimal set of morphological measurands, often termed critical quality attributes (CQAs), which are traceable to standardised (SI) units of measurement. Whilst efforts in defining CQAs have progressed significantly for healthcare applications, there are still numerous measurement challenges associated with image analysis of cultured cells due, in part, to their complex heterogenous nature. This review evaluates the various automated image analysis tools developed for morphological analysis of four commonly considered cell morphological features: the nucleus, actin cytoskeleton, mitochondria, and the cell membrane. The measurement methodologies and outputs from each tool have been evaluated and coinciding outputs have been highlighted as potential CQAs.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1572212"},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182133","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}
引用次数: 0
Hypoxia-driven angiogenesis and metabolic reprogramming in vascular tumors. 血管肿瘤中缺氧驱动的血管生成和代谢重编程。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1572909
Lu Liu, Jiayun Yu, Yang Liu, Liang Xie, Fan Hu, Hanmin Liu
{"title":"Hypoxia-driven angiogenesis and metabolic reprogramming in vascular tumors.","authors":"Lu Liu, Jiayun Yu, Yang Liu, Liang Xie, Fan Hu, Hanmin Liu","doi":"10.3389/fcell.2025.1572909","DOIUrl":"10.3389/fcell.2025.1572909","url":null,"abstract":"<p><p>Hypoxia is a hallmark of the tumor microenvironment (TME), and it plays a crucial role in the occurrence and progression in vascular tumors. Under hypoxic conditions, hypoxia-inducible factor 1-alpha (HIF-1α) is stabilized, inducing changes in the expression of various target genes involved in angiogenesis, metabolism, and cell survival. This includes the upregulation of pro-angiogenic factors like VEGF, which promotes the formation of dysfunctional blood vessels, contributing to the worsening of the hypoxic microenvironment. At the same time, hypoxia induces a metabolic shift toward glycolysis, even in the presence of oxygen, supporting tumor cell survival and proliferation by providing necessary energy and biosynthetic precursors. This review discusses the molecular mechanisms by which hypoxia regulates angiogenesis and metabolic reprogramming in vascular tumors, highlighting the intricate link between these processes, and explores potential therapeutic strategies to target these pathways in order to develop effective treatment strategies for patients.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1572909"},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181472","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}
引用次数: 0
The molecular mechanisms of IUGR programmed adulthood cardiovascular disease. IUGR程序性成人心血管疾病的分子机制
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-15 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1589038
Ting Wu, Wen Zhang, Yangong Wang, Hong Luo, Yifei Li
{"title":"The molecular mechanisms of IUGR programmed adulthood cardiovascular disease.","authors":"Ting Wu, Wen Zhang, Yangong Wang, Hong Luo, Yifei Li","doi":"10.3389/fcell.2025.1589038","DOIUrl":"10.3389/fcell.2025.1589038","url":null,"abstract":"<p><p>Intrauterine growth restriction (IUGR) is secondary to several maternal and fetal adverse conditions. Recently, there is a convincing association between the onset of IUGR and adulthood programmed complications. Among them, the disorders in the cardiovascular system have been revealed by a series of researches. Currently, the prevalence of IUGR is considered to be related to programmed hypertension, coronary artery lesions, pulmonary hypertension, metabolic dysfunction, and even heart failure. According to the emerging knowledge in this field, the experiences of IUGR would induce prolonged inflammation, oxidative injuries, aberrant metabolites and epigenetic regulation, which resulted in endothelial, smooth muscle cells and cardiomyocytes damages. In this review, we summarized the evidences and progress in establishing the association between IUGR and programmed cardiovascular diseases and involved molecular mechanisms. Furthermore, we also discussed the potential efficient therapeutic strategies. This comprehensive review demonstrated that IUGR manifested long-term consequences persisting into adulthood through multifaceted molecular pathways, notably oxidative stress mechanisms, mitochondrial dysfunction, and epigenetic alterations. These findings underscored the critical importance of implementing early preventive interventions and developing personalized therapeutic approaches in future clinical practice.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1589038"},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179887","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}
引用次数: 0
Multiple developmental pathways in organisms with developmentally complex life cycles. 具有复杂生命周期的生物体的多种发育途径。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-14 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1585073
Giuseppe Fusco, Alessandro Minelli
{"title":"Multiple developmental pathways in organisms with developmentally complex life cycles.","authors":"Giuseppe Fusco, Alessandro Minelli","doi":"10.3389/fcell.2025.1585073","DOIUrl":"10.3389/fcell.2025.1585073","url":null,"abstract":"<p><p>One aspect under which an organism's life cycle can be considered complex is when the very same organism can undertake, or obligatorily undertakes, multiple developmental pathways. Examples are organisms with alternation of generations, like most plants, or organisms with reproductive and/or developmental options, like many marine invertebrates. With a broad taxonomic coverage across the eukaryotes, we survey these developmentally complex life cycles, presenting selected case studies to illustrate the relationships between the diverse developmental pathways within the same organism for what concerns morphogenesis and gene expression. We highlight the deep connections between the different types of cycles and show their relationship with phenotypic plasticity, sexual dimorphism and ecological adaptation. The collected materials and organized concepts can provide the basis for future investigations on the disparity of complex life cycles and their evolution across the tree of life.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1585073"},"PeriodicalIF":4.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173339","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}
引用次数: 0
Liquid-liquid phase separation of membrane-less condensates: from biogenesis to function. 无膜凝析液的液-液相分离:从生物起源到功能。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-14 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1600430
Huanyu Guan, Hui Wang, Xin Cai, Jiabo Wang, Zhixin Chai, Jikun Wang, Haibo Wang, Ming Zhang, Zhijuan Wu, Jiangjiang Zhu, Jincheng Zhong, Binglin Yue
{"title":"Liquid-liquid phase separation of membrane-less condensates: from biogenesis to function.","authors":"Huanyu Guan, Hui Wang, Xin Cai, Jiabo Wang, Zhixin Chai, Jikun Wang, Haibo Wang, Ming Zhang, Zhijuan Wu, Jiangjiang Zhu, Jincheng Zhong, Binglin Yue","doi":"10.3389/fcell.2025.1600430","DOIUrl":"10.3389/fcell.2025.1600430","url":null,"abstract":"<p><p>Membrane-less condensates (MLCs) are highly concentrated non-membrane-bounded structures in mammalian cells, comprising heterogeneous mixtures of proteins and/or nucleic acids. As dynamic compartments, MLCs can rapidly exchange components with the cellular environment, and their properties are easily altered in response to environmental signals, thus implicating that they can mediate numerous critical biological functions. A basic understanding of these condensates' formation, function, and underlying biomolecular driving forces has been obtained in recent years. For example, MLCs form through a liquid-liquid phase separation (LLPS) phenomenon similar to polymer condensation, which is primarily maintained via multivalent interactions of multi-domain proteins or proteins harboring intrinsically disordered regions (IDRs) as well as RNAs with binding sites. Moreover, an accumulating body of research indicates that MLCs are pathophysiologically relevant and involved in gene expression regulation and cellular stress responses. Here, we review the emerging field and explore what is currently known about the varied progress in LLPS of MLCs and how their features affect various cellular process, focusing on RNAs, including in skeletal myogenesis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1600430"},"PeriodicalIF":4.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173268","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}
引用次数: 0
M1 macrophage inhibits ferroptosis in Pseudomonas aeruginosa-induced kidney epithelial cell injury through the iNOS/ NO pathway without thiol. M1巨噬细胞通过不含硫醇的iNOS/ NO途径抑制铜绿假单胞菌诱导的肾上皮细胞损伤中的铁凋亡。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-14 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1597160
Peixiang Lu, Xiaojie Bai, Linfa Guo, Kuerban Tuoheti, Shanzhi Zhan, Tongzu Liu
{"title":"M1 macrophage inhibits ferroptosis in <i>Pseudomonas aeruginosa</i>-induced kidney epithelial cell injury through the iNOS/ NO pathway without thiol.","authors":"Peixiang Lu, Xiaojie Bai, Linfa Guo, Kuerban Tuoheti, Shanzhi Zhan, Tongzu Liu","doi":"10.3389/fcell.2025.1597160","DOIUrl":"10.3389/fcell.2025.1597160","url":null,"abstract":"<p><strong>Instruction: </strong>Pseudomonas aeruginosa (PA) is one of the common pathogens of urinary tract infection. It can lead to urosepsis and renal damage. However, the mechanism by which P. aeruginosa affects epithelial cells is not clear.</p><p><strong>Methods: </strong>HK2 cells were treated with extracted PA supernatant (PA.sup). Different pathway inhibitors were added, and similar treatments were applied to HK2 cells co-cultured with macrophages. Cell viability, ferroptosis-related markers, and lipid peroxidation levels were measured.</p><p><strong>Results: </strong>We found that PA induced lipid peroxidation using its specially secreted 15-lipoxygenase (ploxA), thereby triggering ferroptosis in epithelial cells. And PA can also damage the GPx4/GSH defense system of epithelial cells. This effect is not through the proteasome pathway but through activating lysosomal chaperone-mediated autophagy (CMA) to reduce the host's GPx4 expression. Then macrophages inhibited lipid peroxidation and protected cells lacking GPx4/GSH through iNOS/NO•.</p><p><strong>Discussion: </strong>We demonstrated that NO• produced by macrophages can remotely prevent PA-induced ferroptosis of renal epithelial cells. When iNOS, which is responsible for NO• production, is pharmacologically inhibited, the antiferroptotic effect of NO• is reduced. In conclusion, our study reveals an intercellular mechanism for inhibiting ferroptosis, which may provide a new strategy for the host to combat P. aeruginosa -induced ferroptosis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1597160"},"PeriodicalIF":4.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173336","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}
引用次数: 0
Insights into the mechanisms of angiogenesis in hepatoblastoma. 肝母细胞瘤血管生成机制的研究。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-05-14 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1535339
Meng Kong, Yunpeng Zhai, Hongzhen Liu, Shisong Zhang, Shuai Chen, Wenfei Li, Xiang Ma, Yi Ji
{"title":"Insights into the mechanisms of angiogenesis in hepatoblastoma.","authors":"Meng Kong, Yunpeng Zhai, Hongzhen Liu, Shisong Zhang, Shuai Chen, Wenfei Li, Xiang Ma, Yi Ji","doi":"10.3389/fcell.2025.1535339","DOIUrl":"10.3389/fcell.2025.1535339","url":null,"abstract":"<p><p>Hepatoblastoma (HB), the most common pediatric liver malignancy, is characterized by aggressive growth and metastasis driven by complex angiogenic mechanisms. This review elucidates the pivotal role of angiogenesis in HB progression, emphasizing metabolic reprogramming, tumor microenvironment (TME) dynamics, and oncogenic signalling pathways. The Warburg effect in HB cells fosters a hypoxic microenvironment, stabilizing hypoxia-inducible factor-1α (HIF-1α) and upregulating vascular endothelial growth factor (VEGF), which synergistically enhances angiogenesis. Key pathways such as the Wnt/β-catenin, VEGF, PI3K/AKT, and JAK2/STAT3 pathways are central to endothelial cell proliferation, migration, and vascular maturation, whereas interactions with tumor-associated macrophages (TAMs) and pericytes further remodel the TME to support neovascularization. Long noncoding RNAs and glycolytic enzymes have emerged as critical regulators of angiogenesis, linking metabolic activity with vascular expansion. Anti-angiogenic therapies, including VEGF inhibitors and metabolic pathway-targeting agents, show preclinical promise but face challenges such as resistance and off-target effects. Future directions advocate for dual-target strategies, spatial multiomics technologies to map metabolic-angiogenic crosstalk, and personalized approaches leveraging biomarkers for risk stratification. This synthesis underscores the need for interdisciplinary collaboration to translate mechanistic insights into durable therapies, ultimately improving outcomes for HB patients.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1535339"},"PeriodicalIF":4.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173266","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}
引用次数: 0
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