Nature Cell Biology最新文献

CellNavi predicts genes directing cellular transitions by learning a gene graph-enhanced cell state manifold. CellNavi通过学习基因图增强的细胞状态歧管来预测指导细胞转变的基因。

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-10-03 DOI: 10.1038/s41556-025-01755-1

Tianze Wang,Yan Pan,Fusong Ju,Shuxin Zheng,Chang Liu,Yaosen Min,Qun Jiang,Xinwei Liu,Huanhuan Xia,Guoqing Liu,Haiguang Liu,Pan Deng

{"title":"CellNavi predicts genes directing cellular transitions by learning a gene graph-enhanced cell state manifold.","authors":"Tianze Wang,Yan Pan,Fusong Ju,Shuxin Zheng,Chang Liu,Yaosen Min,Qun Jiang,Xinwei Liu,Huanhuan Xia,Guoqing Liu,Haiguang Liu,Pan Deng","doi":"10.1038/s41556-025-01755-1","DOIUrl":"https://doi.org/10.1038/s41556-025-01755-1","url":null,"abstract":"A select few genes act as pivotal drivers in the process of cell state transitions. However, finding key genes involved in different transitions is challenging. Here, to address this problem, we present CellNavi, a deep learning-based framework designed to predict genes that drive cell state transitions. CellNavi builds a driver gene predictor upon a cell state manifold, which captures the intrinsic features of cells by learning from large-scale, high-dimensional transcriptomics data and integrating gene graphs with directional connections. Our analysis shows that CellNavi can accurately predict driver genes for transitions induced by genetic, chemical and cytokine perturbations across diverse cell types, conditions and studies. By leveraging a biologically meaningful cell state manifold, it is proficient in tasks involving critical transitions such as cellular differentiation, disease progression and drug response. CellNavi represents a substantial advancement in driver gene prediction and cell state manipulation, opening new avenues in disease biology and therapeutic discovery.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"6 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215950","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

Author Correction: THY1-mediated mechanisms converge to drive YAP activation in skin homeostasis and repair. 作者更正：thy1介导的机制汇聚在一起，驱动YAP在皮肤稳态和修复中的激活。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-10-02 DOI: 10.1038/s41556-025-01726-6

Egor Sedov, Elle Koren, Sucheta Chopra, Roi Ankawa, Yahav Yosefzon, Marianna Yusupova, Lucien E Weiss, Adnan Mahly, Arad Soffer, Alona Feldman, Chen Luxenburg, Yoav Shechtman, Yaron Fuchs

引用次数: 0

Microtubule architecture connects AMOT stability to YAP/TAZ mechanotransduction and Hippo signalling. 微管结构将AMOT稳定性与YAP/TAZ机械转导和Hippo信号传导联系起来。

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-10-01 DOI: 10.1038/s41556-025-01773-z

Giada Vanni,Anna Citron,Ambela Suli,Paolo Contessotto,Robin Caire,Alessandro Gandin,Giovanna Mantovan,Francesca Zanconato,Giovanna Brusatin,Michele Di Palma,Elisa Peirano,Lisa Sofia Pozzer,Carlo Albanese,Roberto A Steiner,Michelangelo Cordenonsi,Tito Panciera,Stefano Piccolo

{"title":"Microtubule architecture connects AMOT stability to YAP/TAZ mechanotransduction and Hippo signalling.","authors":"Giada Vanni,Anna Citron,Ambela Suli,Paolo Contessotto,Robin Caire,Alessandro Gandin,Giovanna Mantovan,Francesca Zanconato,Giovanna Brusatin,Michele Di Palma,Elisa Peirano,Lisa Sofia Pozzer,Carlo Albanese,Roberto A Steiner,Michelangelo Cordenonsi,Tito Panciera,Stefano Piccolo","doi":"10.1038/s41556-025-01773-z","DOIUrl":"https://doi.org/10.1038/s41556-025-01773-z","url":null,"abstract":"Cellular mechanotransduction is a key informational system, yet its mechanisms remain elusive. Here we unveil the role of microtubules in mechanosignalling, operating downstream of subnuclear F-actin and nuclear envelope mechanics. Upon mechanical activation, microtubules reorganize from a perinuclear cage into a radial array nucleated by centrosomes. This structural rearrangement triggers degradation of AMOT proteins, which we identify as key mechanical rheostats that sequester YAP/TAZ in the cytoplasm. AMOT is stable in mechano-OFF but degraded in mechano-ON cell states, where microtubules allow AMOT rapid transport to the pericentrosomal proteasome in complex with dynein/dynactin. This process ensures swift control of YAP/TAZ function in response to changes in cell mechanics, with experimental loss of AMOT proteins rendering cells insensitive to mechanical modulations. Ras/RTK oncogenes promote YAP/TAZ-dependent tumorigenesis by corrupting this AMOT-centred mechanical checkpoint. Notably, the Hippo pathway fine-tunes mechanotransduction: LATS kinases phosphorylate AMOT, shielding it from degradation, thereby indirectly restraining YAP/TAZ. Thus, AMOT protein stability serves as a hub linking cytoskeletal reorganization and Hippo signalling to YAP/TAZ mechanosignalling.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"99 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203557","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

Remodelling bivalent chromatin is essential for mouse peri-implantation embryogenesis. 重塑二价染色质是小鼠着床期胚胎发生的必要条件。

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-10-01 DOI: 10.1038/s41556-025-01776-w

Yanhe Li,Jincan He,Yingdong Liu,Yi Hui,Shanyao Liu,Yalin Zhang,Yan Xiong,Tingting Xu,Ziwen Xu,Zhuoao Zhang,Yan Zhang,Guang Yang,Jia Zhao,Dandan Bai,Xinyi Lei,Xiaochen Kou,Yanhong Zhao,Jing Du,Zheng Guo,Jiqing Yin,Xiaoqing Zhang,Congling Xu,Yawei Gao,Miaoxin Chen,Hong Wang,Cizhong Jiang,Shaorong Gao,Wenqiang Liu

{"title":"Remodelling bivalent chromatin is essential for mouse peri-implantation embryogenesis.","authors":"Yanhe Li,Jincan He,Yingdong Liu,Yi Hui,Shanyao Liu,Yalin Zhang,Yan Xiong,Tingting Xu,Ziwen Xu,Zhuoao Zhang,Yan Zhang,Guang Yang,Jia Zhao,Dandan Bai,Xinyi Lei,Xiaochen Kou,Yanhong Zhao,Jing Du,Zheng Guo,Jiqing Yin,Xiaoqing Zhang,Congling Xu,Yawei Gao,Miaoxin Chen,Hong Wang,Cizhong Jiang,Shaorong Gao,Wenqiang Liu","doi":"10.1038/s41556-025-01776-w","DOIUrl":"https://doi.org/10.1038/s41556-025-01776-w","url":null,"abstract":"Bivalency regulates developmental genes during lineage commitment. However, mechanisms governing bivalent domain establishment, maintenance and resolution in early embryogenesis remain unclear. Here we comprehensively trace bivalent chromatin remodelling throughout mouse peri-implantation development, revealing bifurcated establishment modes that partition epiblast and primitive endoderm regulatory programmes. We identify transiently maintained bivalent domains (TB domains) enriched in the epiblast, where gradual resolution fine-tunes pluripotency progression. Through targeted screening in embryos, we uncover 22 TB domain regulators, including the essential factor ZBTB17. Genetic ablation or degradation of ZBTB17 causes peri-implantation arrest. Mechanistically, ZBTB17 collaborates with KDM6A/B to resolve bivalency by removing H3K27me3 and priming the activation of key pluripotency genes. Remarkably, TB domain dynamics are evolutionarily shared in human pluripotent transitions, with ZBTB17 involvement despite species differences. Our work establishes a framework for bivalent chromatin regulation in early mammalian development and elucidates how its resolution precisely controls lineage commitment.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"22 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203555","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

Cracking glioblastoma core regulatory codes. 破解胶质母细胞瘤核心调控密码。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-09-30 DOI: 10.1038/s41556-025-01780-0

Yonglong Dang, Yuk Kit Lor, Gonçalo Castelo-Branco

引用次数: 0

Author Correction: ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes. 作者更正：ERCC1-XPF与CTCF和内聚蛋白共同促进印迹基因的发育沉默。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-09-30 DOI: 10.1038/s41556-025-01791-x

Georgia Chatzinikolaou, Zivkos Apostolou, Tamara Aid-Pavlidis, Anna Ioannidou, Ismene Karakasilioti, Giorgio L Papadopoulos, Michalis Aivaliotis, Maria Tsekrekou, John Strouboulis, Theodore Kosteas, George A Garinis

引用次数: 0

Defining heterogeneity in core regulatory circuitry reveals HOXB3 condensation as a potential target in glioblastoma. 定义核心调控回路的异质性揭示HOXB3凝聚是胶质母细胞瘤的潜在靶点。

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-09-30 DOI: 10.1038/s41556-025-01758-y

Chuanxia Zhang,Yijing He,Xiudan Zhan,Jiaming Yu,Shao Xu,Qinkai Zhang,Ru Qiu,Xinyue Wang,Zhuoxing Gao,Meng Huang,Wenyong Long,Qing Liu,Wei Zhao

{"title":"Defining heterogeneity in core regulatory circuitry reveals HOXB3 condensation as a potential target in glioblastoma.","authors":"Chuanxia Zhang,Yijing He,Xiudan Zhan,Jiaming Yu,Shao Xu,Qinkai Zhang,Ru Qiu,Xinyue Wang,Zhuoxing Gao,Meng Huang,Wenyong Long,Qing Liu,Wei Zhao","doi":"10.1038/s41556-025-01758-y","DOIUrl":"https://doi.org/10.1038/s41556-025-01758-y","url":null,"abstract":"Glioblastoma (GBM) exhibits marked heterogeneity, yet therapeutic strategies effectively targeting this variability remain inadequately developed. Here we employed single-cell CUT&Tag analysis to investigate H3K27ac modifications, uncovering pronounced heterogeneity within the core regulatory circuitry (CRC) of GBM. Notably, we observed heterogeneous condensation states of CRC factors, particularly HOXB3, which are shaped by its intrinsically disordered regions and interactions with RUNX1, driving the phenotypic manifestations. Leveraging these findings, we synthesized the peptide P621-R9, which effectively disrupted HOXB3 condensation, altered chromatin structure and reduced transcription at super-enhancer-associated oncogenic sites in GBM cells exhibiting HOXB3 condensation. Treatment with P621-R9 selectively diminished tumourigenic potential in GBM patient-derived xenograft models characterized by HOXB3 condensates, but showed no efficacy in the models lacking these condensates. These results highlight the critical role of CRC condensation in GBM heterogeneity and suggest that peptide-based targeting of distinct GBM subpopulations could represent an avenue for therapeutic exploration.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"97 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194794","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

Phase-separated NDF-FACT condensates facilitate transcription elongation on chromatin. 相分离的NDF-FACT凝聚物促进染色质上的转录延伸。

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-09-30 DOI: 10.1038/s41556-025-01778-8

Ziwei Li,Francesca Burgos-Bravo,Kevin Xu,Chen Li,Kelvin Y Kwan,Alexander B Tong,Zelin Shan,Huan Wang,Motoki Takaku,Joey Li,Zheng Shi,Dmitry Lyumkis,Carlos Bustamante,Jia Fei

{"title":"Phase-separated NDF-FACT condensates facilitate transcription elongation on chromatin.","authors":"Ziwei Li,Francesca Burgos-Bravo,Kevin Xu,Chen Li,Kelvin Y Kwan,Alexander B Tong,Zelin Shan,Huan Wang,Motoki Takaku,Joey Li,Zheng Shi,Dmitry Lyumkis,Carlos Bustamante,Jia Fei","doi":"10.1038/s41556-025-01778-8","DOIUrl":"https://doi.org/10.1038/s41556-025-01778-8","url":null,"abstract":"How the facilitates chromatin transcription (FACT) complex enables RNA polymerase II to overcome chromatin barriers in cells remains poorly understood-especially given the limited direct interactions of FACT with polymerases, DNA or nucleosomes. Here we demonstrate that phase separation, mediated by nucleosome destabilizing factor (NDF), is a key mechanism enabling the function of FACT during transcription elongation. Through biochemical and single-molecule assays, we found that NDF-FACT condensates create specialized biochemical environments that enhance transcription efficiency approximately 20-fold compared with FACT alone. These dynamic condensates form on transcribing RNA polymerase II and travel along chromatin, where they promote efficient nucleosome disassembly at barriers while retaining histones on DNA to preserve chromatin integrity. In human stem cells, disruption of these condensates leads to genome-wide transcriptional defects and chromatin instability, mirroring the effects of FACT depletion. By showing that phase separation enhances FACT function during transcription elongation, our study reveals a key mechanism that preserves chromatin integrity and transcriptional homeostasis in human stem cells.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"32 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194795","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

ER shaping closes the gap in wound healing. ER整形缩小了伤口愈合的间隙。

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2025-09-30 DOI: 10.1038/s41556-025-01779-7

Craig Blackstone

引用次数: 0

Forcing cell fate. 强迫细胞的命运。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2025-09-29 DOI: 10.1038/s41556-025-01775-x

Roberto Mayor

引用次数: 0