Nature Cell Biology最新文献

{"title":"The dual-enhanced graph learning framework DePass allows paired data integration in single-cell and spatial multiomics","authors":"Wei Li, Yuanxiang Jiang, Qingqing Zhao, Yang Xu, Deli Dai, Yu Rong, Xin Zhao, Han Zhang","doi":"10.1038/s41556-026-02067-8","DOIUrl":"10.1038/s41556-026-02067-8","url":null,"abstract":"Recent sequencing advances have enabled abundant multi-omics data generation for both single-cell and spatial contexts. Integrating such multimodal data is critical for decoding cellular and tissue-level complexity. However, compared with single-modality profiling, multimodal data often exhibit higher levels of noise, and existing methods typically overlook this challenge during integration. Meanwhile, most current approaches are tailored to either single-cell or spatial data, limiting their applicability across data types. Here we present DePass, a scalable graph learning framework for paired data integration in both single-cell and spatial multi-omics. We propose a coupled enhancement-integration architecture that iteratively denoises data and improves integrated embeddings. We systematically benchmarked DePass across 6 modalities, 9 tissue types and 13 experimental platforms, demonstrating superior integration accuracy. In the in-house colorectal cancer data, DePass further uncovered immune niche substructure and spatial tumour heterogeneity at near single-cell resolution. These results establish DePass as a unified and generalizable solution for multi-omics integration across diverse biological contexts. Li, Jiang and colleagues present DePass, a graph-based deep learning framework for integrating paired multi-omics data in spatial and single-cell contexts. A dual-enhancement approach is used to remove noise from raw omics data using neighbourhood aggregation.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 10","pages":"2179-2192"},"PeriodicalIF":22.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040025","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":"Author Correction: CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators","authors":"Fatih Aygenli,Lukas A. Huschet,Tanja Popp,Andrea Ribeiro,Darina Barkhatova,Céline Jouffe,Riccardo Trozzo,Jerome S. Menet,Roland Rad,Kenneth A. Dyar,Maciej Lech,Tobias Straub,Alicia K. Michael,Maria S. Robles","doi":"10.1038/s41556-026-02092-7","DOIUrl":"https://doi.org/10.1038/s41556-026-02092-7","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149021192","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":"Author Correction: The bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage","authors":"Xinbo Wang,Peng Xu,Amanda Bentley-DeSousa,William Hancock-Cerutti,Shujun Cai,Benjamin T. Johnson,Francesca Tonelli,Lin Shao,Gabriel Talaia,Dario R. Alessi,Shawn M. Ferguson,Pietro De Camilli","doi":"10.1038/s41556-026-02094-5","DOIUrl":"https://doi.org/10.1038/s41556-026-02094-5","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"17 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149021191","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":"Author Correction: Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy","authors":"Mariya Licheva,Jeremy Pflaum,Riccardo Babic,Hector Mancilla,Jana Elsässer,Emily Boyle,David M. Hollenstein,Jorge Jimenez-Niebla,Jonas Pleyer,Mio Heinrich,Franz-Georg Wieland,Joachim Brenneisen,Christopher Eickhorst,Johann Brenner,Shan Jiang,Markus Hartl,Sonja Welsch,Carola Hunte,Jens Timmer,Florian Wilfling,Claudine Kraft","doi":"10.1038/s41556-026-02095-4","DOIUrl":"https://doi.org/10.1038/s41556-026-02095-4","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"154 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149021190","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":"Lysosomes enlist endoplasmic reticulum microdomains for repair","authors":"Zhengyang An, Song Dang, Kangmin He","doi":"10.1038/s41556-026-02064-x","DOIUrl":"10.1038/s41556-026-02064-x","url":null,"abstract":"Maintaining lysosomal membrane integrity is essential for lysosomal function and cellular homeostasis. A study now describes a lysosome repair mechanism, in which phosphatidylinositol 3-phosphate and DFCP1 accumulation at endoplasmic reticulum (ER) microdomains drives focal enrichment of the lipid channel protein VPS13C at ER–lysosome contact sites to promote lysosomal repair.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 10","pages":"1989-1990"},"PeriodicalIF":22.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149021189","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":"Author Correction: Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.","authors":"Daqi Li, Gaoyuan Cui, Kailin Yang, Chenfei Lu, Yuhan Jiang, Le Zhang, Qiulian Wu, Deobrat Dixit, Zhe Zhu, Ryan C Gimple, Danling Gu, Jiancheng Gao, Qiankun Lin, Hang Yu, Zhumei Shi, Yun Chen, Qianghu Wang, Guangfu Jin, Fan Lin, Junfei Shao, Qigang Zhou, Chong Liu, Chaojun Li, Yongping You, Nu Zhang, Junxia Zhang, Xu Qian, Qian Zhang, Jeremy N Rich, Xiuxing Wang","doi":"10.1038/s41556-026-02083-8","DOIUrl":"https://doi.org/10.1038/s41556-026-02083-8","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":" ","pages":""},"PeriodicalIF":22.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983223","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":"Immune cells go with the tissue flow","authors":"Salik Miskat Borbora, Milka Sarris","doi":"10.1038/s41556-026-02077-6","DOIUrl":"10.1038/s41556-026-02077-6","url":null,"abstract":"During development and regeneration, tissues undergo large-scale remodelling and it remains unclear how such morphogenetic movements influence immune cell guidance. A study by Le et al. shows that ectodermal tissue flow affects the movement of embryonic myeloid cells during the early stages of Xenopus development.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 10","pages":"1987-1988"},"PeriodicalIF":22.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983218","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":"The Batten disease protein CLN8 is a stereospecific acyltransferase in bis(monoacylglycero)phosphate biosynthesis","authors":"Pradeep K. Sheokand, Denis Lacabanne, Andrew M. James, Stefania Della Vecchia, Jonathan J. Ruprecht, Joris van der Kleij, Keira Turner, Jessica Müller-Niva, Miia H. Salo, Benjamin Jenkins, Susannah K. Leese, Nidhi Juneja, Chak Shun Yu, Clarissa D. Booth, Martin S. King, Johanna Uusimaa, Jill M. Weimer, Albert Koulman, Reetta Hinttala, Filippo M. Santorelli, Maria Marchese, Michael P. Murphy, Edmund R. S. Kunji, Kasparas Petkevicius","doi":"10.1038/s41556-026-02061-0","DOIUrl":"10.1038/s41556-026-02061-0","url":null,"abstract":"Loss-of-function mutations in the endoplasmic reticulum membrane protein CLN8 cause Batten disease, a neurodegenerative lysosomal storage disorder. CLN8 acts with the lysosomal enzyme CLN5 to produce bis(monoacylglycero)phosphate (BMP), a signature lysosomal phospholipid with unique S,S stereochemistry. However, the role of CLN8 in this pathway has remained unclear. Here we establish that CLN8 is a glycerophosphoglycerol acyltransferase that catalyses the stereospecific acylation of S,S-glycerophosphoglycerol to generate S,S-lysophosphatidylglycerol, the CLN5 substrate in BMP synthesis. Cryo-electron microscopy structures define the CLN8 active site and support a ping-pong acyl transfer mechanism. Batten disease mutations impair CLN8 enzymatic activity and abolish BMP production in mice. Exogenous S,S-lysophosphatidylglycerol, but not the R,S stereoisomer, restores BMP synthesis in CLN8-deficient cells and mice and improves neurological phenotypes in cln8 mutant zebrafish. These findings define the function of CLN8, explain the biochemical basis of CLN8 Batten disease and establish BMP precursor supplementation as a proof-of-concept therapeutic strategy. Two studies show that the endoplasmic reticulum-associated protein CLN8 catalyses the acyl CoA-dependent acylation of glycerophosphoglycerol, producing lysophosphatidylglycerol, which is then converted into bis(monoacylglycero)phosphate. These results provide insight into CLN8 Batten disease.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 10","pages":"2068-2077"},"PeriodicalIF":22.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-02061-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977310","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":"CLN8 recycles glycerol backbones for BMP","authors":"Zhengyue Cao, Cunqi Ye","doi":"10.1038/s41556-026-02069-6","DOIUrl":"10.1038/s41556-026-02069-6","url":null,"abstract":"Two studies identify CLN8 as a glycerophosphoglycerol acyltransferase that generates the lysophosphatidylglycerol precursor for CLN5-mediated bis(monoacylglycero)phosphate (BMP) biosynthesis. These findings define a key upstream step in BMP synthesis and raise fundamental questions about lipid recycling and metabolic feedback.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 10","pages":"1991-1992"},"PeriodicalIF":22.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977243","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":"DFCP1-containing ER microdomains mediate lysosomal membrane repair","authors":"Maja Radulovic, Sascha Pust, Athanasios Kournoutis, Di Chen, M. Isabel Giner, Qijian Liang, Santosh Phuyal, Thomas J. Böddeker, Katy McCarron, Eric Herrmann, Kevin Rose, Sebastian W. Schultz, Andreas Brech, James H. Hurley, Claudio Bussi, Luis Bonet-Ponce, Maximiliano G. Gutierrez, Camilla Raiborg, Harald Stenmark","doi":"10.1038/s41556-026-02062-z","DOIUrl":"10.1038/s41556-026-02062-z","url":null,"abstract":"Lysosomal membrane integrity is essential for preserving cellular homeostasis in response to different stressors. Upon lysosomal membrane permeabilization, cells activate several mechanisms for lysosomal membrane repair, including ESCRT proteins, phosphatidylinositol 4-phosphate (PI4P)-dependent lipid transfer from the endoplasmic reticulum (ER) and conjugation of ATG8 family proteins to single membranes (CASM). The interplay between these pathways and the regulation of the lipid transfer machinery remain incompletely understood. Here we show that phosphatidylinositol 3-phosphate (PI3P)-containing ER domains play a major role in lysosomal membrane repair. PI3P is formed on lysosome-proximal ER domains by the phosphatidylinositol 3-kinase PIK3C3/VPS34 in response to membrane damage, and inhibition or depletion of PIK3C3 inhibits lysosome repair. Mechanistically, the ATPase DFCP1/ZFYVE1 accumulates on lysosome-proximal ER domains by its PI3P binding, triggered by Ca2+ efflux from lysosomes and requiring the ULK1 kinase complex and ER proteins of the VAP family. Downstream of CASM, PI4P, ESCRTs and PI3P, DFCP1 promotes focal accumulation of the lipid channel VPS13C on ER domains proximal to damaged lysosomes to promote their repair. The function and dynamics of DFCP1 depend on its ability to bind and hydrolyse ATP, and absence of DFCP1 compromises cellular resistance to vacuolar damage induced by Listeria monocytogenes. We conclude that DFCP1 mediates concentration of the ER-associated lipid transport machinery at damaged lysosomes to promote their sealing in response to Ca2+ flux and PIK3C3 activation. Radulovic et al. show that phosphatidylinositol 3-phosphate (PI3P), produced by the phosphatidylinositol 3-kinase PIK3C3, is formed on ER domains after lysosome damage. ER domain PI3P helps to recruit the ATPase DFCP1, which promotes lysosome repair.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 10","pages":"2036-2053"},"PeriodicalIF":22.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-02062-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977295","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}