Nature Cell Biology最新文献_第6页

Discovery of a multi-chaperone condensate in the endoplasmic reticulum 内质网中多伴侣凝聚物的发现

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-20 DOI: 10.1038/s41556-025-01731-9

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Systematic decoding of functional enhancer connectomes and risk variants in human glioma 人类胶质瘤中功能增强子连接体和风险变异的系统解码。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-19 DOI: 10.1038/s41556-025-01737-3

Jinfang Bi, Weipeng Mo, Man Liu, Yingjie Song, Qian Xiao, Sibo Fan, Wenbin Wang, Tengfei Shi, Yaoqiang Zheng, Jie Lian, Rong Liu, Bohan Chen, Xiaofeng Huang, Peng Li, Zhongfang Zhao, Jiandang Shi, Lei Zhang, Guangsong Su, Nu Zhang, Wange Lu

{"title":"Systematic decoding of functional enhancer connectomes and risk variants in human glioma","authors":"Jinfang Bi, Weipeng Mo, Man Liu, Yingjie Song, Qian Xiao, Sibo Fan, Wenbin Wang, Tengfei Shi, Yaoqiang Zheng, Jie Lian, Rong Liu, Bohan Chen, Xiaofeng Huang, Peng Li, Zhongfang Zhao, Jiandang Shi, Lei Zhang, Guangsong Su, Nu Zhang, Wange Lu","doi":"10.1038/s41556-025-01737-3","DOIUrl":"10.1038/s41556-025-01737-3","url":null,"abstract":"Genetic and epigenetic variations contribute to the progression of glioma, but the mechanisms underlying these effects, particularly for enhancer-associated genetic variations in non-coding regions, still remain unclear. Here we performed high-throughput CRISPR interference screening to identify pro-tumour enhancers in glioma cells. By integrating genome-wide H3K27ac HiChIP data, we identified the target genes of these pro-tumour enhancers and revealed the essential role of enhancer connectomes in promoting glioma progression. Through systematic analysis of enhancers carrying glioma risk-associated single-nucleotide polymorphisms (SNPs), we found that these SNPs can promote glioma progression through the enhancer connectome. Using CRISPR–Cas9-mediated enhancer interference and SNP editing, we demonstrated that glioma-specific enhancer carrying the risk SNP rs2297440 regulates SOX18 expression by specifically recruiting transcription factor MEIS1 binding, thereby contributing to glioma progression. Our study sheds light on the molecular mechanisms underlying glioma susceptibility and provides potential therapeutic targets to treat glioma. Bi, Mo, Liu et al. carry out high-throughput screening and analysis to profile genome-wide pro-tumour enhancers and uncover enhancer connectomes in glioma. In particular, they identify specific single-nucleotide polymorphisms associated with glioma risk and progression.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 10","pages":"1838-1847"},"PeriodicalIF":19.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-025-01737-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883234","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}

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Author Correction: PD-1 signalling defines and protects leukaemic stem cells from T cell receptor-induced cell death in T cell acute lymphoblastic leukaemia 作者更正：PD-1信号在T细胞急性淋巴细胞白血病中定义和保护白血病干细胞免受T细胞受体诱导的细胞死亡。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-19 DOI: 10.1038/s41556-025-01761-3

Xi Xu, Wenwen Zhang, Li Xuan, Yanhui Yu, Wen Zheng, Fang Tao, Jacqelyn Nemechek, Chong He, Weiwei Ma, Xue Han, Siyu Xie, Minyi Zhao, Jian Wang, Yuhua Qu, Qifa Liu, John M. Perry, Linjia Jiang, Meng Zhao

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Edge curvature drives endoplasmic reticulum reorganization and dictates epithelial migration mode 边缘曲率驱动内质网重组并决定上皮迁移模式。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-18 DOI: 10.1038/s41556-025-01729-3

Simran Rawal, Pradeep Keshavanarayana, Diya Manoj, Purnati Khuntia, Sanak Banerjee, Basil Thurakkal, Rituraj Marwaha, Fabian Spill, Tamal Das

{"title":"Edge curvature drives endoplasmic reticulum reorganization and dictates epithelial migration mode","authors":"Simran Rawal, Pradeep Keshavanarayana, Diya Manoj, Purnati Khuntia, Sanak Banerjee, Basil Thurakkal, Rituraj Marwaha, Fabian Spill, Tamal Das","doi":"10.1038/s41556-025-01729-3","DOIUrl":"10.1038/s41556-025-01729-3","url":null,"abstract":"From single-cell extrusion to centimetre-sized wounds, epithelial gaps of various sizes and geometries appear across organisms. Their closure involves two orthogonal modes: lamellipodial crawling at convex edges and purse string-like movements at concave edges. The mechanisms driving this curvature-dependent migration remain unclear. Here we perform an intracellular cartography to reveal that in both micropatterned and naturally arising gaps, the endoplasmic reticulum (ER) undergoes edge curvature-dependent morphological reorganizations, forming tubules at convex edges and sheets at concave edges. This reorganization depends on cytoskeleton-generated protrusive and contractile forces. Mathematical modelling reveals that these morphologies minimize strain energy under their respective geometric regime. Functionally, ER tubules at the convex edge favour perpendicularly oriented focal adhesions, supporting lamellipodial crawling, while ER sheets at the concave edge favour parallelly oriented focal adhesions, supporting purse string-like movements. Altogether, ER emerges as a central mechanotransducer, integrating signals from cytoskeletal networks to orchestrate two orthogonal modes of cell migration. Rawal et al. combine intracellular cartography and biophysical modelling to reveal how edge curvature governs endoplasmic reticulum (ER) morphology, showing that curvature-dependent ER reorganization directs distinct modes of epithelial cell migration.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 10","pages":"1660-1675"},"PeriodicalIF":19.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-025-01729-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874140","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}

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Morula-derived trophectoderm stem cells 桑葚衍生的滋养外胚层干细胞

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-14 DOI: 10.1038/s41556-025-01733-7

Daisuke Suzuki, Yasuhiro Takashima

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Mouse trophectoderm stem cells generated with morula signalling inducers capture an early trophectoderm state 用桑葚信号诱导剂生成的小鼠滋养外胚层干细胞捕获早期滋养外胚层状态

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-14 DOI: 10.1038/s41556-025-01732-8

Yake Gao, Mingying Li, Wei Guan, Wei Guo, Shu Wei, Fang Yan, Wenrui Han, Xueting Zhang, Tong Yin, Yunkun Dang, Huanhuan Li, José C. R. Silva, Jian Zhang

{"title":"Mouse trophectoderm stem cells generated with morula signalling inducers capture an early trophectoderm state","authors":"Yake Gao, Mingying Li, Wei Guan, Wei Guo, Shu Wei, Fang Yan, Wenrui Han, Xueting Zhang, Tong Yin, Yunkun Dang, Huanhuan Li, José C. R. Silva, Jian Zhang","doi":"10.1038/s41556-025-01732-8","DOIUrl":"10.1038/s41556-025-01732-8","url":null,"abstract":"The first embryonic cell differentiation in mice segregates the trophectoderm and the inner cell mass. Successful derivation of mouse trophoblast stem cells (TSCs) and trophectoderm stem cells (TESCs) has greatly facilitated the understanding of trophoblast differentiation. However, our understanding of early trophectoderm differentiation remains incomplete. Here we report the establishment of a morula-derived trophectoderm stem cell (MTSC) line from 32-cell embryos that show enhanced and uniform trophoblast core gene expression. Importantly, distinct from TSCs or TESCs, MTSCs represent a much earlier trophectoderm state (E3.5) than that of TSCs (E5.5–6.5) and TESCs (E4.5–5.5). MTSCs can robustly integrate into all cell lineages of the placenta. Moreover, MTSCs can self-organize to form placenta organoids. When partially differentiated MTSCs aggregate with embryonic stem cells, they form blastoids that efficiently implant uteruses. Finally, MSTC medium can efficiently convert embryonic stem cells, TSCs and TESCs into MTSC-like cells. Thus, MTSCs capture an early blastocyst trophectoderm state and provide a research model for studying trophoblast development. Gao, Li and colleagues derive trophectoderm stem cells from 32-cell mouse embryos. These cells represent an early trophectoderm state and are capable of developing into placenta cells, forming placental organoids and contributing to blastoid generation.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 9","pages":"1572-1586"},"PeriodicalIF":19.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840131","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}

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Metabolic regulation of RIPK1 RIPK1的代谢调控

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-11 DOI: 10.1038/s41556-025-01742-6

Zhe Wang

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A multichaperone condensate enhances protein folding in the endoplasmic reticulum 多伴侣蛋白凝聚体增强了内质网中的蛋白质折叠

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-11 DOI: 10.1038/s41556-025-01730-w

Anna Leder, Guillaume Mas, Viktória Szentgyörgyi, Roman P. Jakob, Timm Maier, Anne Spang, Sebastian Hiller

{"title":"A multichaperone condensate enhances protein folding in the endoplasmic reticulum","authors":"Anna Leder, Guillaume Mas, Viktória Szentgyörgyi, Roman P. Jakob, Timm Maier, Anne Spang, Sebastian Hiller","doi":"10.1038/s41556-025-01730-w","DOIUrl":"10.1038/s41556-025-01730-w","url":null,"abstract":"Protein folding in the endoplasmic reticulum (ER) relies on a network of molecular chaperones that facilitates the folding and maturation of client proteins. How the ER chaperones organize in a supramolecular manner to exert their cooperativity has, however, remained unclear. Here we report the discovery of a multichaperone condensate in the ER lumen, which is formed around the chaperone PDIA6 during protein folding homeostasis. The condensates form in a Ca2+-dependent manner and we resolve the underlying mechanism at the atomic and cellular levels. The PDIA6 condensates recruit further chaperones—Hsp70 BiP, J-domain protein ERdj3, disulfide isomerase PDIA1 and Hsp90 Grp94—which constitute some of the essential components of the early folding machinery. The chaperone condensates enhance folding of proteins, such as proinsulin, and prevent protein misfolding in the ER lumen. The PDIA6-scaffolded chaperone condensates hence provide the functional basis for spatial and temporal coordination of the dynamic ER chaperone network. Leder et al. show that the chaperones PDIA6, Hsp70 BiP, ERdj3, PDIA1 and Hsp90 form co-condensates within the endoplasmic reticulum, enhancing folding and preventing misfolding of client proteins.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 9","pages":"1422-1430"},"PeriodicalIF":19.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-025-01730-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813005","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}

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The liver metabolizes dietary galactose to fuel antitumour T cell immunity 肝脏代谢饮食中的半乳糖来促进抗肿瘤T细胞免疫

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-11 DOI: 10.1038/s41556-025-01717-7

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A SETD2–CDK1–lamin axis maintains nuclear morphology and genome stability setd2 - cdk1 -纤层蛋白轴维持核形态和基因组稳定性

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-08-11 DOI: 10.1038/s41556-025-01723-9

Abid Khan, Cheng Zhang, Phu G. Nguyen, James M. Metts, Lucas C. Collins, Kanishk Jain, C. Allie Mills, Logan Vlach, Kelin Li, Amanda L. Brademeyer, Brittany M. Bowman, Michael B. Major, Jeffrey Aubé, Laura E. Herring, W. Kimryn Rathmell, Frank M. Mason, Ian J. Davis, Qing Zhang, Brian D. Strahl

{"title":"A SETD2–CDK1–lamin axis maintains nuclear morphology and genome stability","authors":"Abid Khan, Cheng Zhang, Phu G. Nguyen, James M. Metts, Lucas C. Collins, Kanishk Jain, C. Allie Mills, Logan Vlach, Kelin Li, Amanda L. Brademeyer, Brittany M. Bowman, Michael B. Major, Jeffrey Aubé, Laura E. Herring, W. Kimryn Rathmell, Frank M. Mason, Ian J. Davis, Qing Zhang, Brian D. Strahl","doi":"10.1038/s41556-025-01723-9","DOIUrl":"10.1038/s41556-025-01723-9","url":null,"abstract":"Histone methyltransferases regulate chromatin organization and are frequently mutated in human diseases, including cancer. One such often mutated methyltransferase, SETD2, associates with transcribing RNA polymerase II and catalyses H3K36me3—a modification that contributes to gene transcription, splicing and DNA repair. Although its catalytic function is well-characterized, its non-catalytic roles remain unclear. Here we reveal a catalysis-independent function of SETD2 in nuclear lamina stability and genome integrity. Through its intrinsically disordered amino terminus, SETD2 associates with lamina-associated proteins, including lamin A/C, lamin B1 and emerin. Loss of SETD2 or its N terminus leads to severe nuclear morphology defects and genome instability, mirroring lamina dysfunction. Mechanistically, the N terminus of SETD2 serves as a scaffold for the mitotic kinase CDK1 and lamins, facilitating lamin phosphorylation and depolymerization during mitosis. Restoration of the N-terminal regions required for interaction with CDK1 and lamins rescues nuclear morphology and suppresses tumorigenic growth in a clear cell renal cell carcinoma model with SETD2 haploinsufficiency. These findings reveal a previously unrecognized role of SETD2 in nuclear lamina organization and genome maintenance that probably extends to its role as a tumour suppressor. Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associate with lamins during nuclear-envelope disassembly","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"27 8","pages":"1327-1341"},"PeriodicalIF":19.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812929","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}

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