Frontiers in Cell and Developmental Biology最新文献

筛选
英文 中文
Differences in neuronal ciliation rate and ciliary content revealed by systematic imaging-based analysis of hiPSC-derived models across protocols. 不同方案hipsc衍生模型的系统成像分析揭示了神经元调解率和纤毛含量的差异。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-11 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1516596
Walther Haenseler, Melanie Eschment, Beth Evans, Marta Brasili, Joana Figueiro-Silva, Fee Roethlisberger, Affef Abidi, Darcie Jackson, Martin Müller, Sally A Cowley, Ruxandra Bachmann-Gagescu
{"title":"Differences in neuronal ciliation rate and ciliary content revealed by systematic imaging-based analysis of hiPSC-derived models across protocols.","authors":"Walther Haenseler, Melanie Eschment, Beth Evans, Marta Brasili, Joana Figueiro-Silva, Fee Roethlisberger, Affef Abidi, Darcie Jackson, Martin Müller, Sally A Cowley, Ruxandra Bachmann-Gagescu","doi":"10.3389/fcell.2025.1516596","DOIUrl":"https://doi.org/10.3389/fcell.2025.1516596","url":null,"abstract":"<p><strong>Introduction: </strong>Ciliopathies are a group of human Mendelian disorders caused by dysfunction of primary cilia, small quasi-ubiquitous sensory organelles. Patients suffering from ciliopathies often display prominent neurodevelopmental phenotypes, underscoring the importance of primary cilia during development and for function of the central nervous system (CNS). Human tissues, in particular from the CNS, are very hard to obtain for research. Patient derived- or genetically engineered human induced pluripotent stem cells (hiPSCs) are therefore a precious resource for investigating the role of cilia in human neurons.</p><p><strong>Methods: </strong>In this study we used a variety of 2D and 3D neuronal differentiation protocols in multiple hiPSC lines and systematically analyzed ciliation rates and ciliary length in hiPSCs, neural stem cells (NSCs), immature and different types of mature neurons using immunofluorescence.</p><p><strong>Results: </strong>We found that ciliation rate varied substantially between cell lines and differentiation protocols. Moreover, ciliation rate depended on differentiation stage, being maximal in NSCs and decreasing with neuronal maturation. In various types of mature neurons obtained with different protocols, we found ciliation rates to be as low as ∼10%. Neuronal density also played an important role, with higher ciliation in denser cultures. We further investigated the ciliary protein content in these cells at different differentiation stages using commonly used antibodies against ARL13B, INPP5E, AC3 and GPR161. Cilia in hiPSCs, NSCs and neurons were all positive for ARL13B, with a decreasing trend in intensity in more mature neurons. Likewise, INPP5E was present in all cilia analyzed, while AC3 positivity increased as maturation proceeded. Interestingly, we found that while GPR161 signal almost completely disappeared from cilia upon Sonic hedgehog (SHH) stimulation in NSCs and immature neurons, this was not the case in more mature neurons, suggesting a possible developmental time window for cilia-dependent SHH signaling.</p><p><strong>Conclusion: </strong>Taken together, our results provide a systematic description of cilia in hiPSC-derived neuronal cells generated with different protocols, underscoring the importance of selecting the optimal model system and controls for investigating primary cilia in hiPSC-derived neuronal cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1516596"},"PeriodicalIF":4.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977261","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
Assessing the prognostic and therapeutic value of cuproptosis-related genes in colon adenocarcinoma patients. 评估结肠腺癌患者铜倾相关基因的预后和治疗价值。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-10 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1550982
Zhanhui Ye, Yixian Song, Mengqing Zhu, Fuying Zheng, Wenjie Qin, Xue Li, Pei Wang, Zihua Li, Kequan Chen, Aimin Li
{"title":"Assessing the prognostic and therapeutic value of cuproptosis-related genes in colon adenocarcinoma patients.","authors":"Zhanhui Ye, Yixian Song, Mengqing Zhu, Fuying Zheng, Wenjie Qin, Xue Li, Pei Wang, Zihua Li, Kequan Chen, Aimin Li","doi":"10.3389/fcell.2025.1550982","DOIUrl":"https://doi.org/10.3389/fcell.2025.1550982","url":null,"abstract":"<p><strong>Background: </strong>Colon adenocarcinoma (COAD) remains a major global health challenge with poor prognosis despite advances in treatment, underscoring the need for new biomarkers. As a novel mode of cell death, cuproptosis is thought to be potentially involved in the development of cancer. However, the particularly as the role of cuproptosis-related genes (CRGs) in COAD prognosis and therapy remains unclear.</p><p><strong>Methods: </strong>We analyzed RNA sequencing data from The Cancer Genome Atlas for COAD, focusing on CRG expression patterns and their clinicopathological correlations. Using the Weighted Gene Co-expression Network Analysis (WGCNA) method, we identified the gene module most strongly linked to cuproptosis and conducted functional enrichment analysis to explore the roles of genes within this module in COAD tumorigenesis. A novel prognostic risk model based on four CRGs (ORC1, PTTG1, DLAT, PDHB) was developed to stratify COAD patients into high-risk and low-risk groups, assessing overall survival, tumor microenvironment, and mutational landscape differences. We also evaluated the therapeutic effects of ferredoxin 1 (FDX1) and elesclomol in promoting cuproptosis in HCT116 and LoVo cell lines through various experiments, including cell proliferation, apoptosis assessment, mitochondrial membrane potential evaluation, and DLAT lipoylation detection via Western blot.</p><p><strong>Results: </strong>Certain CRGs showed different expressions in COAD <i>versus</i> normal tissues. WGCNA identified a gene module linked to cuproptosis, crucial for pathways like cell cycle regulation, citrate cycle (TCA cycle), and DNA replication. The novel risk model stratified patients into high and low-risk groups based on risk scores, revealing that high-risk COAD patients had shorter overall survival and distinct immune cell infiltration, while low-risk patients were more sensitive to immunotherapy. Experimental results indicated that FDX1 exerted an inhibitory effect on COAD, and its combination with elesclomol significantly reduced proliferation, promoted apoptosis, increased DLAT lipoylation, and lowered mitochondrial membrane potential in COAD cells.</p><p><strong>Conclusion: </strong>The findings of this study provided a new perspective for the research on biomarkers and therapeutic strategies in COAD, evaluated the prognostic and therapeutic value of CRGs in COAD patients, and laid a theoretical foundation for the future clinical application of CRGs.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1550982"},"PeriodicalIF":4.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991703","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
Metabolomic profiling and biomarker identification for early detection and therapeutic targeting of doxorubicin-induced cardiotoxicity. 代谢组学分析和生物标志物鉴定用于阿霉素诱导的心脏毒性的早期检测和治疗靶向。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-10 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1543636
Jingjing Ding, Xianzhen Feng, Zhongqing Xu, Hong Xu
{"title":"Metabolomic profiling and biomarker identification for early detection and therapeutic targeting of doxorubicin-induced cardiotoxicity.","authors":"Jingjing Ding, Xianzhen Feng, Zhongqing Xu, Hong Xu","doi":"10.3389/fcell.2025.1543636","DOIUrl":"https://doi.org/10.3389/fcell.2025.1543636","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is a widely used chemotherapeutic agent known for its efficacy against various cancers, but its clinical application is often limited by its cardiotoxic effects. The exact mechanisms of DOX-induced cardiotoxicity remain unclear, requiring further investigation. Early diagnosis is essential to enhance the quality of life and prognosis for patients with malignancies. This study aims to identify biomarkers and therapeutic targets for DOX cardiotoxicity.</p><p><strong>Methods: </strong>Heart tissue samples from 20 DOX-treated cardiotoxic mice and 19 normal controls were analyzed using liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analysis identified differential metabolites. Key metabolites were assessed using a random forest algorithm, and ROC curves evaluated diagnostic value. H9C2 rat cardiomyoblast cells were cultured to investigate the protective effects of these metabolites.</p><p><strong>Results: </strong>Among 291 metabolites, significant differences emerged between cardiotoxic and normal mice. Five metabolites-4-hydroxy-valeric acid, 2-methylbutanoic acid, traumatic acid, PI (18:2 (9Z, 12Z)/0:0), and MIPC (t18:0/24:0 (2OH))-showed diagnostic potential. ROC analysis indicated excellent value for 4-hydroxy-valeric acid and PI (18:2 (9Z, 12Z)/0:0) and high discriminatory power for 2-methylbutanoic acid (AUC = 0. 99). Pathway analysis highlighted glycosylphosphatidylinositol-anchor biosynthesis, unsaturated fatty acids biosynthesis, pantothenate and CoA pathways, among others, associated with DOX-induced cardiotoxicity. In addition, we found that the differential metabolite Cer (d18:0/12:0) can improve DOX-induced myocardial cell damage and inhibit apoptosis-related protein expression at the cellular level.</p><p><strong>Conclusion: </strong>Heart tissue metabolomics with LC-MS identified critical metabolites and pathways associated with DOX cardiotoxicity, suggesting biomarkers for early diagnosis and potential therapeutic targets to mitigate DOX-related cardiotoxicity and improve clinical outcomes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1543636"},"PeriodicalIF":4.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003519","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
Slit-Robo signaling supports motor neuron avoidance of the spinal cord midline through DCC antagonism and other mechanisms. Slit-Robo信号通过DCC拮抗和其他机制支持运动神经元对脊髓中线的回避。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-10 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1563403
Kelsey R Nickerson, Ferass M Sammoura, Yonghong Zhou, Alexander Jaworski
{"title":"Slit-Robo signaling supports motor neuron avoidance of the spinal cord midline through DCC antagonism and other mechanisms.","authors":"Kelsey R Nickerson, Ferass M Sammoura, Yonghong Zhou, Alexander Jaworski","doi":"10.3389/fcell.2025.1563403","DOIUrl":"https://doi.org/10.3389/fcell.2025.1563403","url":null,"abstract":"<p><p>Axon pathfinding and neuronal migration are orchestrated by attractive and repulsive guidance cues. In the mouse spinal cord, repulsion from Slit proteins through Robo family receptors and attraction to Netrin-1, mediated by the receptor DCC, control many aspects of neural circuit formation. This includes motor neuron wiring, where Robos help prevent both motor neuron cell bodies and axons from aberrantly crossing the spinal cord midline. These functions had been ascribed to Robo signaling being required to counter DCC-mediated attraction to Netrin-1 at the midline, either by mediating repulsion from midline-derived Slits or by silencing DCC signaling. However, the role of DCC in promoting motor neuron and axon midline crossing had not been directly tested. Here, we used <i>in vivo</i> mouse genetics and <i>in vitro</i> axon turning assays to further explore the interplay between Slit and Netrin signaling in motor neuron migration and axon guidance relative to the midline. We find that DCC is a major driver of midline crossing by motor axons, but not motor neuron cell bodies, when <i>Robo1</i> and <i>Robo2</i> are knocked out. Further, <i>in vitro</i> results indicate that Netrin-1 attracts motor axons and that Slits can modulate the chemotropic response to Netrin-1, converting it from attraction to repulsion. Our findings indicate that Robo signaling allows both motor neuron cell bodies and axons to avoid the midline, but that only motor axons require this pathway to antagonize DCC-dependent midline attraction, which likely involves a combination of mediating Slit repulsion and directly influencing Netrin-DCC signaling output.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1563403"},"PeriodicalIF":4.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991717","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
Retinol-binding protein 4 in skeletal and cardiac muscle: molecular mechanisms, clinical implications, and future perspectives. 骨骼肌和心肌中的视黄醇结合蛋白4:分子机制、临床意义和未来展望
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-10 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1587165
Kangzhen Zhang, Lijuan Wang, Wei Gao, Rong Guo
{"title":"Retinol-binding protein 4 in skeletal and cardiac muscle: molecular mechanisms, clinical implications, and future perspectives.","authors":"Kangzhen Zhang, Lijuan Wang, Wei Gao, Rong Guo","doi":"10.3389/fcell.2025.1587165","DOIUrl":"https://doi.org/10.3389/fcell.2025.1587165","url":null,"abstract":"<p><p>Retinol-binding protein 4 (RBP4) has emerged as a critical adipokine involved in the pathophysiology of metabolic and cardiovascular diseases. Beyond its classical role in retinol transport, RBP4 influences insulin resistance, inflammation, lipid metabolism, mitochondrial function, and cellular apoptosis in both skeletal and cardiac muscles. Elevated levels of RBP4 are associated with obesity, type 2 mellitus diabetes, and cardiovascular diseases, making it a potential biomarker and therapeutic target. This comprehensive review elucidates the molecular mechanisms by which RBP4 affects skeletal and cardiac muscle physiology. We discuss its clinical implications as a biomarker for disease risk and progression, explore therapeutic strategies targeting RBP4, and highlight future research directions. Understanding the multifaceted roles of RBP4 could pave the way for novel interventions against metabolic and cardiovascular disorders.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1587165"},"PeriodicalIF":4.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003522","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
Loss of vitamin D receptor induces premature ovarian insufficiency through compromising the 7-dehydrocholesterol-dependent anti-aging effects. 维生素D受体的丧失通过损害7-脱氢胆固醇依赖的抗衰老作用而导致卵巢早衰。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-10 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1545167
Haiyun Chen, Qiuyi Wang, Yi Zhang, Luxi Shangguan, Zhengquan Zhu, Huan Zhang, Xiang Zou, Qinghe Geng, Yanting Wen, Daojuan Wang, Yong Wang
{"title":"Loss of vitamin D receptor induces premature ovarian insufficiency through compromising the 7-dehydrocholesterol-dependent anti-aging effects.","authors":"Haiyun Chen, Qiuyi Wang, Yi Zhang, Luxi Shangguan, Zhengquan Zhu, Huan Zhang, Xiang Zou, Qinghe Geng, Yanting Wen, Daojuan Wang, Yong Wang","doi":"10.3389/fcell.2025.1545167","DOIUrl":"https://doi.org/10.3389/fcell.2025.1545167","url":null,"abstract":"<p><p>Vitamin D has the potential to therapeutically affect the endocrine parameters of premature ovarian insufficiency (POI) patients. Previous research has indicated that serum vitamin D levels tend to decline with age and in individuals with POI. However, the precise impact of vitamin D deficiency on female fertility, especially their ovarian function, remains unclear. Vitamin D receptor (VDR) deficiency mice provide a model to investigate the possible effect of vitamin D on female reproduction. In this study, we observed abnormal follicular development in the <i>Vdr</i> deficiency mice. This anomaly is associated with reduced expression of anti-Mullerian hormone (AMH) and disrupted aromatase expression that disrupts the hormone secretion. Moreover, our findings indicate that <i>Vdr</i> deficiency disturbs redox balance, resulting in oxidative stress in the ovary, which further suppresses granulosa cell function and accelerates ovarian aging. Mechanistically, loss of <i>Vdr</i> inhibits <i>de novo</i> cholesterol synthesis by transcriptional repression of <i>Hmgcr</i>, and the antioxidant and anti-aging effects of the intermediate product 7-dehydrocholesterol (7-DHC) are also decreased. Treatment with 7-DHC effectively reduces ROS levels and alleviates aging in KGN cells deficient in <i>Vdr</i>. In conclusion, our results show that <i>Vdr</i> deficiency impairs follicle maturation and hormone secretion by accelerating granulosa cell aging, as a result of the reduced antioxidant and anti-aging effect of 7-DHC.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1545167"},"PeriodicalIF":4.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991715","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
Wnt5a and Notum influence the temporal dynamics of cartilaginous mesenchymal condensations in developing trachea. Wnt5a和Notum影响气管发育过程中软骨间充质凝聚的时间动力学。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-09 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1523833
Natalia Bottasso-Arias, Megha Mohanakrishnan, Sarah Trovillion, Kaulini Burra, Nicholas X Russell, Yixin Wu, Yan Xu, Debora Sinner
{"title":"Wnt5a and Notum influence the temporal dynamics of cartilaginous mesenchymal condensations in developing trachea.","authors":"Natalia Bottasso-Arias, Megha Mohanakrishnan, Sarah Trovillion, Kaulini Burra, Nicholas X Russell, Yixin Wu, Yan Xu, Debora Sinner","doi":"10.3389/fcell.2025.1523833","DOIUrl":"https://doi.org/10.3389/fcell.2025.1523833","url":null,"abstract":"<p><strong>Introduction: </strong>The trachea is essential for proper airflow to the lungs for gas exchange. Frequent congenital tracheal malformations affect the cartilage, causing the collapse of the central airway during the respiratory cycle. We have shown that Notum, a Wnt ligand de-acylase that attenuates the canonical branch of the Wnt signaling pathway, is necessary for cartilaginous mesenchymal condensations. In Notum deficient tracheas, chondrogenesis is delayed, and the tracheal lumen is narrowed. It is unknown if Notum attenuates non-canonical Wnt signaling. We observed premature tracheal chondrogenesis after mesenchymal deletion of the non-canonical Wnt5a ligand. We hypothesize that Notum and Wnt5a are required to mediate the timely formation of mesenchymal condensations, giving rise to the tracheal cartilage.</p><p><strong>Methods/results: </strong><i>Ex vivo</i> culture of tracheal tissue shows that chemical inhibition of the Wnt non-canonical pathway promotes earlier condensations, while Notum inhibition presents delayed condensations. Furthermore, non-canonical Wnt induction prevents the formation of cartilaginous mesenchymal condensations. On the other hand, cell-cell interactions among chondroblasts increase in the absence of mesenchymal Wnt5a. By performing an unbiased analysis of the gene expression in Wnt5a and Notum deficient tracheas, we detect that by E11.5, mRNA of genes essential for chondrogenesis and extracellular matrix formation are upregulated in Wnt5a mutants. The expression profile supports the premature and delayed chondrogenesis observed in Wnt5a and Notum deficient tracheas, respectively.</p><p><strong>Conclusion: </strong>We conclude that Notum and Wnt5a are necessary for proper tracheal cartilage patterning by coordinating timely chondrogenesis. Thus, these studies shed light on molecular mechanisms underlying congenital anomalies of the trachea.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1523833"},"PeriodicalIF":4.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960295","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
Summary of the mechanism of ferroptosis regulated by m6A modification in cancer progression. 肿瘤进展中m6A修饰调控铁凋亡机制综述。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-09 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1507171
Bin Fan, Gangxian Chen, Shuyi Huang, Ying Li, Zia Ul Haq Nabil, Zuozhang Yang
{"title":"Summary of the mechanism of ferroptosis regulated by m6A modification in cancer progression.","authors":"Bin Fan, Gangxian Chen, Shuyi Huang, Ying Li, Zia Ul Haq Nabil, Zuozhang Yang","doi":"10.3389/fcell.2025.1507171","DOIUrl":"https://doi.org/10.3389/fcell.2025.1507171","url":null,"abstract":"<p><p>The most common form of internal RNA modification in eukaryotes is called n6-methyladenosine (m6A) methylation. It has become more and more well-known as a research issue in recent years since it alters RNA metabolism and is involved in numerous biological processes. Currently, m6A alteration offers new opportunities in clinical applications and is intimately linked to carcinogenesis. Ferroptosis-a form of iron-dependent, lipid peroxidation-induced regulated cell death-was discovered. In the development of cancer, it has become an important factor. According to newly available data, ferroptosis regulates tumor growth, and cancer exhibits aberrant m6A levels in crucial ferroptosis regulatory components. On the other hand, m6A has multiple roles in the development of tumors, and the relationship between m6A-modified ferroptosis and malignancies is quite intricate. In this review, we first give a thorough review of the regulatory and functional roles of m6A methylation, focusing on the molecular processes of m6A through the regulation of ferroptosis in human cancer progression and metastasis, which are strongly associated to cancer initiation, progression, and drug resistance. Therefore, it is crucial to clarify the relationship between m6A-mediated regulation of ferroptosis in cancer progression, providing a new strategy for cancer treatment with substantial clinical implications.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1507171"},"PeriodicalIF":4.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985884","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
Engineered mesenchymal stromal cells with interleukin-1beta sticky-trap attenuate osteoarthritis in knee joints. 白细胞介素-1 -粘附诱捕的工程间充质间质细胞可减轻膝关节骨关节炎。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-08 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1559155
Christopher Kim, Biao Li, Sayaka Nakamura, Eric J Neely, Jason S Rockel, Tatiana Oussenko, Puzheng Zhang, Mohit Kapoor, Andras Nagy
{"title":"Engineered mesenchymal stromal cells with interleukin-1beta sticky-trap attenuate osteoarthritis in knee joints.","authors":"Christopher Kim, Biao Li, Sayaka Nakamura, Eric J Neely, Jason S Rockel, Tatiana Oussenko, Puzheng Zhang, Mohit Kapoor, Andras Nagy","doi":"10.3389/fcell.2025.1559155","DOIUrl":"https://doi.org/10.3389/fcell.2025.1559155","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common chronic inflammatory joint disease, in which innate immunity plays a pivotal role in pathogenesis. Anti-interleukin-1(IL-1) therapies have shown inconsistent results in clinical trials, potentially due to a mismatch in the spatial and temporal dynamics of interleukin-1beta (IL-1β) production and therapeutic interventions. To address this issue, we developed a novel IL-1β \"sticky-trap\" utilizing cell and gene-based technologies from our lab and evaluated its efficacy in reducing osteoarthritis progression using a murine destabilization of the medial meniscus (DMM) OA model and a compact bone-derived mesenchymal stromal cell (MSC)-based gene expression system. The extracellular domain of interleukin-1 receptor 2 (IL1R2) was employed to design the sticky IL1R2 trap (stkIL1R2). A murine compact bone-derived MSC line was engineered for gene delivery. Although stkIL1R2 was undetectable in the engineered MSC supernatants by enzyme-linked immunosorbent assay (ELISA) and Western blot, it was localized on the cell surface and extracellular matrix (ECM) and demonstrated specific binding to IL-1β using a fluorescent protein-fused binding assay. Doxycycline (Dox)-induced expression of stkIL1R2 significantly inhibited lipocalin-2 (LCN2) expression which is a biomarker of IL-1β activity. For <i>in vivo</i> experiments, 5 × 10<sup>4</sup> Dox-inducible stkIL1R2f expressing MSCs were injected into the knee joints of DMM mice. Bioluminescence imaging revealed MSC survival in the knee joints for up to 7 weeks post-injection. Histological analyses at 10 weeks post-injection, including Safranin-O and Masson trichrome staining, showed that stkIL1R2 treated joints exhibited significantly less cartilage degradation and synovitis compared to controls, as assessed by Osteoarthritis Research Society International (OARSI) scoring of the femur, tibia, and synovium. Moreover, stkIL1R2 treatment reduced matrix metalloproteinases-13 (MMP-13) positive cells and collagen type II degradation in the affected joints. In conclusion, we developed a MSC line expressing an inducible IL1 sticky-trap, which localized to the cell surface and ECM and specifically bound IL-1β. These engineered MSCs survived in normal and DMM knee joints for up to 7 weeks and significantly delayed OA progression and inflammation in the murine model. This study introduces a promising therapeutic approach to combat OA progression.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1559155"},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994999","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
Addressing the tissue specificity of U5 snRNP spliceosomopathies. 解决U5 snRNP剪接肌病的组织特异性。
IF 4.6 2区 生物学
Frontiers in Cell and Developmental Biology Pub Date : 2025-04-08 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1572188
Rahmat Azhari Kemal, Raymond T O'Keefe
{"title":"Addressing the tissue specificity of U5 snRNP spliceosomopathies.","authors":"Rahmat Azhari Kemal, Raymond T O'Keefe","doi":"10.3389/fcell.2025.1572188","DOIUrl":"https://doi.org/10.3389/fcell.2025.1572188","url":null,"abstract":"<p><p>Precursor mRNA (pre-mRNA) must undergo splicing to remove intron sequences and join exons. This splicing process is catalysed by an RNA/protein complex called the spliceosome. At the centre of the catalytic spliceosome is the U5 small nuclear ribonucleoprotein (snRNP). Pathogenic variants in U5 snRNP core proteins are associated with various diseases commonly known as spliceosomopathies. Variants in <i>TXNL4A</i> and <i>EFTUD2</i> manifest in craniofacial malformations while variants in <i>PRPF8</i> and <i>SNRNP200</i> manifest in retinitis pigmentosa. This perspective highlights research addressing how these specific manifestations come about as the spliceosome is required in all cells and at all developmental stages. Cell and animal models can replicate the human clinical specificity providing explanations for the specificity of the disorders. We propose that future research could benefit from models originating from patient-derived induced pluripotent stem cells (iPSCs) and isogenic controls to compare the coding and non-coding transcriptomic perturbations. Analysis of spliceosomal protein complexes and their interactome could also uncover novel insights on molecular pathogenesis. Finally, as studies highlight changes in metabolic processes, metabolomic studies could become a new venture in studying the consequences of U5 snRNP variants.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1572188"},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991230","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信