Nature Cell Biology最新文献

{"title":"Differentiation, ageing and leukaemia alter the metabolic profile of human bone marrow haematopoietic stem and progenitor cells","authors":"Maria-Eleni Lalioti, Mari Carmen Romero-Mulero, Noémie Karabacz, Julian Mess, Helen Demollin, Jasmin Rettkowski, Konrad Schuldes, Michael Mitterer, Carolin Wadle, Khalid Shoumariyeh, Mirijam Egg, Carlos Alfonso-Gonzalez, Karin Jäcklein, Katharina Schönberger, Nikolaos Karantzelis, Gregor Reisig, Philipp Aktories, Isabella M. Mayer, Ioanna Tsoukala, Alexander Schäffer, Irene Tirado-Gonzalez, Aurélien Dugourd, Lukas M. Braun, Beatriz Silva-Rego, Michael-Jason Jones, Katrin Kierdorf, Julio Saez-Rodriguez, Kilian Reising, Sebastian Gottfried Walter, Hind Medyouf, Valérie Hilgers, Gabriel Ghiaur, Robert Zeiser, Darja Karpova, Simon Renders, Sascha Gravius, Joerg Buescher, Nina Cabezas-Wallscheid","doi":"10.1038/s41556-025-01709-7","DOIUrl":"10.1038/s41556-025-01709-7","url":null,"abstract":"Metabolic cues are crucial for regulating haematopoietic stem and progenitor cells (HSPCs). However, the metabolic profile of human HSPCs remains poorly understood due to the limited number of cells and the scarcity of bone marrow samples. Here we present the integrated metabolome, lipidome and transcriptome of human adult HSPCs (lineage−, CD34+, CD38−) upon differentiation, ageing and acute myeloid leukaemia. The combination of low-input targeted metabolomics with our newly optimized low-input untargeted lipidomics workflow allows us to detect up to 193 metabolites and lipids from a starting material of 3,000 and 5,000 HSPCs, respectively. Among other findings, we observe elevated levels of the essential nutrient choline in HSPCs compared with downstream progenitors, which decline upon ageing and further decrease in acute myeloid leukaemia. Functionally, we show that choline supplementation fuels lipid production in HSPCs and enhances stemness. Overall, our study provides a comprehensive resource identifying metabolic changes that can be utilized to promote and enhance human stem cell function. Lalioti, Romero-Mulero et al. combine metabolomics, lipidomics and transcriptomics of haematopoietic stem and progenitor cells during differentiation, ageing and leukaemia, finding a role for choline and showing that supplementation enhances stemness.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 8","pages":"1367-1380"},"PeriodicalIF":19.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-025-01709-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane signalling directs chromatin remodelling","authors":"Sabrya Carim","doi":"10.1038/s41556-025-01714-w","DOIUrl":"10.1038/s41556-025-01714-w","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 7","pages":"1054-1054"},"PeriodicalIF":19.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629708","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}

{"title":"Lipoprotein in ferroptosis regulation","authors":"Zhe Wang","doi":"10.1038/s41556-025-01719-5","DOIUrl":"10.1038/s41556-025-01719-5","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 7","pages":"1054-1054"},"PeriodicalIF":19.1,"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}

{"title":"Phosphoinositide flipping governs neomycin sensitivity","authors":"Michael Salsaa, Gregory D. Fairn","doi":"10.1038/s41556-025-01707-9","DOIUrl":"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":"27 7","pages":"1057-1058"},"PeriodicalIF":19.1,"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}

{"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":"10.1038/s41556-025-01696-9","url":null,"abstract":"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. Hu et al. use single-cell RNA sequencing to explore the transcriptional profile of human amnion samples spanning the developmental window from Carnegie stage (CS)16 to CS23.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 7","pages":"1175-1185"},"PeriodicalIF":19.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-025-01696-9.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coming out is not a one-time event","authors":"Stylianos Lefkopoulos, Jan Żylicz","doi":"10.1038/s41556-025-01702-0","DOIUrl":"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":"27 7","pages":"1052-1053"},"PeriodicalIF":19.1,"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}

{"title":"Revealing the order of chromatin reorganization events with Dam&ChIC","authors":"","doi":"10.1038/s41556-025-01710-0","DOIUrl":"10.1038/s41556-025-01710-0","url":null,"abstract":"Epigenetic states are formed by the coordinated activity of several chromatin factors. Dam&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":"27 7","pages":"1061-1062"},"PeriodicalIF":19.1,"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}

{"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":"10.1038/s41556-025-01692-z","url":null,"abstract":"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, NEO1 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. Jain et al. report that the Neo1 P4-ATPase flips the lipid PI4P across the Golgi membrane to the cytosolic leaflet, preventing PI4P exposure and thereby conferring neomycin resistance.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 7","pages":"1114-1124"},"PeriodicalIF":19.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-025-01692-z.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bridge-like lipid transport protein controls plasma membrane lipid composition and fluidity","authors":"","doi":"10.1038/s41556-025-01680-3","DOIUrl":"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":"27 7","pages":"1059-1060"},"PeriodicalIF":19.1,"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}

{"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":"10.1038/s41556-025-01687-w","url":null,"abstract":"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&ChIC, a method that enables retrospective and multifactorial chromatin profiling in single cells. Dam&ChIC employs chromatin labelling in living cells with m6A 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&ChIC provides retrospective single-cell chromatin data. When applied in random X chromosome inactivation, Dam&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&ChIC will be instrumental in unravelling the interconnectivity and order of gene-regulatory events underlying cell-state changes during development. Kefalopoulou, Rullens et al. develop Dam&ChIC to assay chromatin state at two different time points in the same cell. The method was used to study the reorganization of LADs during cell division and X chromosome inactivation.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 7","pages":"1186-1198"},"PeriodicalIF":19.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-025-01687-w.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}