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Lipoprotein in ferroptosis regulation 脂蛋白在铁下垂调节中的作用
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-14 DOI: 10.1038/s41556-025-01719-5
Zhe Wang
{"title":"Lipoprotein in ferroptosis regulation","authors":"Zhe Wang","doi":"10.1038/s41556-025-01719-5","DOIUrl":"https://doi.org/10.1038/s41556-025-01719-5","url":null,"abstract":"<p>In addition to intracellular de novo synthesis, tumour cells acquire lipids via the uptake of extracellular lipoproteins, but the underlying mechanism and its functional consequences remain unclear. A study now reports uptake of lipoproteins as a defence mechanism against ferroptosis in cancer.</p><p>The authors started with a pooled CRISPR screen and identified <i>GPX4</i> as the most essential gene in lipoprotein-depleted cultures of HeLa cells. They then confirmed that both low-density and high-density lipoproteins mitigated ferroptosis in various cancer cell lines. Further genetic screens targeting metabolic genes and transporters revealed sulfated glycosaminoglycans (GAG) as modulators of lipoprotein uptake and ferroptosis resistance in cancer cells. In mice with Karpas299 tumours, GAG depletion with by heparinase and chondroitinase increased lipid peroxidation and reduced tumour growth. The authors then observed increased levels of chondroitin sulfate and lipoprotein-derived α-tocopherol in human kidney tumours. Lastly, using patient-derived xenografts, they confirmed the role for GAGs in mediating lipoprotein uptake and tumour progression.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"109 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phosphoinositide flipping governs neomycin sensitivity 磷酸肌肽翻转控制新霉素敏感性
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-14 DOI: 10.1038/s41556-025-01707-9
Michael Salsaa, Gregory D. Fairn
{"title":"Phosphoinositide flipping governs neomycin sensitivity","authors":"Michael Salsaa, Gregory D. Fairn","doi":"10.1038/s41556-025-01707-9","DOIUrl":"https://doi.org/10.1038/s41556-025-01707-9","url":null,"abstract":"Neomycin toxicity in eukaryotic cells stems from its binding to phosphoinositides, primarily confined to the inner leaflet of the plasma membrane. New research reveals a complex lipid-trafficking pathway that exposes phosphatidylinositol 4-phosphate on the cell surface and identifies Neo1 as a flippase that limits this exposure.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"60 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Atlas of amnion development during the first trimester of human pregnancy 人类怀孕前三个月羊膜发育图谱
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-14 DOI: 10.1038/s41556-025-01696-9
Wenqi Hu, Carmen Sancho-Serra, Carlos W. Gantner, Hanna M. Szafranska, Nita Solanky, Kate Metcalfe, Roser Vento-Tormo, Magdalena Zernicka-Goetz
{"title":"Atlas of amnion development during the first trimester of human pregnancy","authors":"Wenqi Hu, Carmen Sancho-Serra, Carlos W. Gantner, Hanna M. Szafranska, Nita Solanky, Kate Metcalfe, Roser Vento-Tormo, Magdalena Zernicka-Goetz","doi":"10.1038/s41556-025-01696-9","DOIUrl":"https://doi.org/10.1038/s41556-025-01696-9","url":null,"abstract":"<p>The amnion is a critical extra-embryonic structure that supports foetal development, yet its ontogeny remains poorly defined. Here, using single-cell transcriptomics, we identified major cell types and subtypes in the human amnion across the first trimester of pregnancy, broadly categorized into epithelial, mesenchymal and macrophage lineages. We uncovered epithelial–mesenchymal and epithelial–immune transitions, highlighting dynamic remodelling during early pregnancy. Our results further revealed key intercellular communication pathways, including BMP4 signalling from mesenchymal to epithelial cells and TGF-β signalling from macrophages to mesenchymal cells, suggesting coordinated interactions that drive amnion morphogenesis. In addition, integrative comparisons across humans, non-human primates and in vitro stem cell-based models reveal that stem cell-based models recapitulate various stages of amnion development, emphasizing the need for careful selection of model systems to accurately recapitulate in vivo amnion formation. Collectively, our findings provide a detailed view of amnion cellular composition and interactions, advancing our understanding of its developmental role and regenerative potential.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"50 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coming out is not a one-time event 出柜不是一次性的
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-14 DOI: 10.1038/s41556-025-01702-0
Stylianos Lefkopoulos, Jan Żylicz
{"title":"Coming out is not a one-time event","authors":"Stylianos Lefkopoulos, Jan Żylicz","doi":"10.1038/s41556-025-01702-0","DOIUrl":"https://doi.org/10.1038/s41556-025-01702-0","url":null,"abstract":"June is the month celebrating Pride in the USA and other countries around the world to honour the Stonewall Uprising of 1969, as well as all progress and current strives claiming equal justice for members of the LGBTQIA+ community. In this piece, we are talking to Jan Żylicz, associate professor and group leader at Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, about the importance of celebrating Pride, his views on representation in science and his personal scientific journey as a member of the LGBTQIA+ community.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"47 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Revealing the order of chromatin reorganization events with Dam&ChIC 用Dam&ChIC揭示染色质重组事件的顺序
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-14 DOI: 10.1038/s41556-025-01710-0
{"title":"Revealing the order of chromatin reorganization events with Dam&ChIC","authors":"","doi":"10.1038/s41556-025-01710-0","DOIUrl":"https://doi.org/10.1038/s41556-025-01710-0","url":null,"abstract":"Epigenetic states are formed by the coordinated activity of several chromatin factors. Dam&amp;ChIC recovers both past and current epigenetic states in single cells, revealing the timing and order of chromatin reorganization. It enabled us to identify how spatial chromatin localization is inherited upon mitosis, and to dissect successive chromatin remodeling events during the initiation of X-chromosome inactivation.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"68 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
P4-ATPases control phosphoinositide membrane asymmetry and neomycin resistance p4 - atp酶控制磷酸肌苷膜不对称和新霉素耐药性
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-11 DOI: 10.1038/s41556-025-01692-z
Bhawik K. Jain, H. Diessel Duan, Christina Valentine, Ariana Samiha, Huilin Li, Todd R. Graham
{"title":"P4-ATPases control phosphoinositide membrane asymmetry and neomycin resistance","authors":"Bhawik K. Jain, H. Diessel Duan, Christina Valentine, Ariana Samiha, Huilin Li, Todd R. Graham","doi":"10.1038/s41556-025-01692-z","DOIUrl":"https://doi.org/10.1038/s41556-025-01692-z","url":null,"abstract":"<p>The aminoglycoside antibiotic neomycin has robust antibacterial properties, yet its clinical utility is curtailed by its nephrotoxicity and ototoxicity. The mechanism by which the polycationic neomycin enters specific eukaryotic cell types remains poorly understood. In budding yeast, <i>NEO1</i> is required for neomycin resistance and encodes a phospholipid flippase that establishes membrane asymmetry. Here we show that mutations altering Neo1 substrate recognition cause neomycin hypersensitivity by exposing phosphatidylinositol-4-phosphate (PI4P) in the plasma membrane extracellular leaflet. Cryogenic electron microscopy reveals PI4P binding to Neo1 within the substrate translocation pathway. PI4P enters the lumen of the endoplasmic reticulum and is flipped by Neo1 at the Golgi to prevent PI4P secretion to the cell surface. Deficiency of the orthologous ATP9A in human cells also causes exposure of PI4P and neomycin sensitivity. These findings unveil conserved mechanisms of aminoglycoside sensitivity and phosphoinositide homoeostasis, with important implications for signalling by extracellular phosphoinositides.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"22 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A bridge-like lipid transport protein controls plasma membrane lipid composition and fluidity 桥状脂质转运蛋白控制质膜脂质的组成和流动性
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-11 DOI: 10.1038/s41556-025-01680-3
{"title":"A bridge-like lipid transport protein controls plasma membrane lipid composition and fluidity","authors":"","doi":"10.1038/s41556-025-01680-3","DOIUrl":"https://doi.org/10.1038/s41556-025-01680-3","url":null,"abstract":"BLTP2 is a bridge-like lipid transport protein that operates at contacts between the endoplasmic reticulum and the plasma membrane. We show that phosphatidylethanolamine is transported to the plasma membrane by BLTP2, where it maintains membrane fluidity. Depletion of BLTP2 significantly impaired the metastasis of a triple-negative breast cancer cell line in xenografts.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"93 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retrospective and multifactorial single-cell profiling reveals sequential chromatin reorganization during X inactivation 回顾性和多因子单细胞分析揭示了X失活过程中染色质的顺序重组
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-10 DOI: 10.1038/s41556-025-01687-w
Samy Kefalopoulou, Pim M. J. Rullens, Kim L. de Luca, Sandra S. de Vries, Tessy Korthout, Alexander van Oudenaarden, Peter Zeller, Jop Kind
{"title":"Retrospective and multifactorial single-cell profiling reveals sequential chromatin reorganization during X inactivation","authors":"Samy Kefalopoulou, Pim M. J. Rullens, Kim L. de Luca, Sandra S. de Vries, Tessy Korthout, Alexander van Oudenaarden, Peter Zeller, Jop Kind","doi":"10.1038/s41556-025-01687-w","DOIUrl":"https://doi.org/10.1038/s41556-025-01687-w","url":null,"abstract":"<p>The regulation of gene expression is governed at multiple levels of chromatin organization. However, how gene regulation is co-ordinated remains relatively unexplored. Here we develop Dam&amp;ChIC, a method that enables retrospective and multifactorial chromatin profiling in single cells. Dam&amp;ChIC employs chromatin labelling in living cells with <sup>m6</sup>A to acquire a past chromatin state, coupled with an antibody-mediated readout to capture the present chromatin state. Analyses of diverse factor combinations highlight its versatility and superior resolution. By tracking lamina-associated domain inheritance over the cell cycle, we showcase that Dam&amp;ChIC provides retrospective single-cell chromatin data. When applied in random X chromosome inactivation, Dam&amp;ChIC disentangles the temporal order of chromatin remodelling events. Upon mitotic exit and following Xist expression, the inactive X chromosome undergoes extensive genome–lamina detachment, preceding spreading of Polycomb. We anticipate that Dam&amp;ChIC will be instrumental in unravelling the interconnectivity and order of gene-regulatory events underlying cell-state changes during development.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"153 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Never let you go 永远不会让你离开
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-07 DOI: 10.1038/s41556-025-01724-8
Angela R. Parrish
{"title":"Never let you go","authors":"Angela R. Parrish","doi":"10.1038/s41556-025-01724-8","DOIUrl":"https://doi.org/10.1038/s41556-025-01724-8","url":null,"abstract":"<p>Abscission is the final step of cell division, typically occurring within 1–2 hours of furrow closure, although extended connections have been observed previously. In a recent report, Vasilev et al. show that in early mouse embryos, attachment between daughter cells are maintained much longer than in somatic cells, which allows cytoplasmic molecules to diffuse between them.</p><p>To determine how long the cytokinetic bridge was maintained after division, the authors injected photoactivatable GFP into one cell of a 4-cell stage developing mouse embryo and imaged the cells to 32-cell stage. Transfer occurs throughout interphase and ends once the microtubules maintaining the bridge disappear. Further analysis of early embryos identified a requirement of Aurora kinase to maintain these extensions, and the authors characterized the types of molecules that can be exchanged. Although these connections did not affect cell fate decisions, they did support the synchronous apoptosis of the linked cells by diffusion of apoptosis regulators.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"111 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An overview of contemporary theories of ageing 当代老龄化理论概述
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-07-01 DOI: 10.1038/s41556-025-01698-7
João Pedro de Magalhães
{"title":"An overview of contemporary theories of ageing","authors":"João Pedro de Magalhães","doi":"10.1038/s41556-025-01698-7","DOIUrl":"https://doi.org/10.1038/s41556-025-01698-7","url":null,"abstract":"<p>Ageing is a complex biological process whose underlying mechanisms remain contentious. Nonetheless, due to an ageing global population and the rising incidence of age-related diseases, understanding why we age is one of the most important scientific questions of our time, with profound medical implications. Here, I explore the fundamental nature of the ageing process and provide an overview of modern mechanistic theories. I critically examine two main groups of ageing theories: error-based and program-based theories. I discuss the relevance of these theories in the context of ageing patterns, genetic manipulations and longevity drugs, highlighting how experimental challenges and technological limitations have hindered progress. Overall, there is a pressing and unmet need for a robust theoretical framework in ageing research. Elucidating the cellular and molecular mechanisms of ageing would be crucial for developing effective interventions that slow the ageing process and prevent its associated diseases.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"25 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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