Nature Cell Biology最新文献_第7页

CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators CLOCK/BMAL1相互作用组揭示同源结构域因子作为组织调节因子。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-08-06 DOI: 10.1038/s41556-026-02041-4

Fatih Aygenli, Lukas A. Huschet, Tanja Popp, Andrea Ribeiro, Darina Barkhatova, Céline Jouffe, Ricardo Trozzo, Jerome S. Menet, Roland Rad, Kenneth A. Dyar, Maciej Lech, Tobias Straub, Alicia K. Michael, Maria S. Robles

{"title":"CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators","authors":"Fatih Aygenli, Lukas A. Huschet, Tanja Popp, Andrea Ribeiro, Darina Barkhatova, Céline Jouffe, Ricardo Trozzo, Jerome S. Menet, Roland Rad, Kenneth A. Dyar, Maciej Lech, Tobias Straub, Alicia K. Michael, Maria S. Robles","doi":"10.1038/s41556-026-02041-4","DOIUrl":"10.1038/s41556-026-02041-4","url":null,"abstract":"Circadian clocks underlie daily rhythms in physiology by coordinating temporal patterns of gene expression and protein function throughout the body. At the core of this system in mammals is CLOCK/BMAL1, a ubiquitously expressed heterodimeric transcription factor complex that orchestrates tissue-specific circadian gene expression. The basis for this specificity remains unclear, but tissue-specific interactions at chromatin could provide one. Here we used chromatin immunoprecipitation coupled to mass spectrometry to map CLOCK/BMAL1-associated protein complexes on chromatin in mouse liver, kidney and lung. We detected 1,510 associated proteins, most of which were tissue-specific and not explained by protein abundance. Among these, we identified the homeodomain transcription factors PROX1, HNF1B and HOXA5 as tissue-enriched interactors that bind BMAL1, co-occupy most BMAL1 genomic sites and establish organ-restricted circadian transcription. Our findings demonstrate that tissue-specific transcription factors confer cellular identity on the core clock, thereby contributing to organ-specific patterns of rhythmic gene expression. Aygenli et al. map chromatin-bound CLOCK/BMAL1 protein complexes across three mouse tissues and uncover PROX1, HNF1B and HOXA5 as homeodomain cofactors that directly bind and co-occupy BMAL1 sites to establish tissue-specific circadian transcription.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 9","pages":"1890-1900"},"PeriodicalIF":22.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-02041-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685270","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}

引用次数: 0

Stromal cell senescence augments haematopoietic cell fitness in clonal haematopoiesis 基质细胞衰老增强了克隆造血中造血细胞的适应性。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-08-06 DOI: 10.1038/s41556-026-02025-4

Jayna J. Mistry, Kira A. Young, Anna Navarro Figueredo, Gibran Edun, Alicia G. Aguilar-Navarro, Patricia A. Colom Díaz, Maria Telpoukhovskaia, Inés Fernández Maestre, Sheng F. Cai, Katharina S. Götze, Anastasia N. Tikhonova, Ross L. Levine, Jennifer J. Trowbridge

{"title":"Stromal cell senescence augments haematopoietic cell fitness in clonal haematopoiesis","authors":"Jayna J. Mistry, Kira A. Young, Anna Navarro Figueredo, Gibran Edun, Alicia G. Aguilar-Navarro, Patricia A. Colom Díaz, Maria Telpoukhovskaia, Inés Fernández Maestre, Sheng F. Cai, Katharina S. Götze, Anastasia N. Tikhonova, Ross L. Levine, Jennifer J. Trowbridge","doi":"10.1038/s41556-026-02025-4","DOIUrl":"10.1038/s41556-026-02025-4","url":null,"abstract":"Microenvironment remodelling impacts tumour growth and metastasis, but whether remodelling promotes pre-malignant clonal fitness remains unknown. Here, using single-cell RNA-sequencing of the bone-marrow microenvironment in a mouse model of DNMT3A-mutant clonal haematopoiesis (CH), we identify mesenchymal stromal cells (MSCs) in a molecular state of cellular senescence. Elevated bone-marrow MSC senescence is also observed in humans with CH driven by several common somatic mutations. MSC senescence is induced by mutant haematopoietic cells in a contact-independent manner through production of soluble factors including TNF-α and IL-6. These cytokines activate a Stat3-driven pathway that is necessary and sufficient for MSC senescence induction. Genetic or pharmacological depletion of senescent non-haematopoietic cells reduces the burden of CH and delays progression to myeloid neoplasia. Our findings show that microenvironment remodelling modifies pre-malignant clonal fitness and identifies disruption of the crosstalk between pre-malignant cells and their niche as a cancer prevention strategy. Mistry et al. propose that Dnmt3a-mutant haematopoietic cells induce mesenchymal stromal cell senescence. Removal of senescent non-haematopoietic cells reduces Dnmt3a-mutant haematopoiesis.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 8","pages":"1656-1670"},"PeriodicalIF":22.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-02025-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685244","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}

引用次数: 0

Author Correction: Targeting liquid–liquid phase separation of SARS-CoV-2 nucleocapsid protein promotes innate antiviral immunity by elevating MAVS activity 作者更正：靶向液-液相分离SARS-CoV-2核衣壳蛋白通过提高MAVS活性促进先天抗病毒免疫。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-08-05 DOI: 10.1038/s41556-026-02056-x

Shuai Wang, Tong Dai, Ziran Qin, Ting Pan, Feng Chu, Lingfeng Lou, Long Zhang, Bing Yang, Huizhe Huang, Huasong Lu, Fangfang Zhou

引用次数: 0

BRD4 recruitment into HP1 condensates desilences transcription without erasure of repressive chromatin BRD4被募集到HP1凝集会使转录沉默，但不会消除抑制染色质。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-08-05 DOI: 10.1038/s41556-026-02044-1

Christopher J. Brandon, Sarah Robinson-Thiewes, Mangesh Kaulage, Wojciech Rosikiewicz, Matthew J. Cuneo, Joseph Brett, Jindpreet Kandola, Walter H. Lang, Jonathan Low, Ashraf Mohammed, Adithi Danda, Sam Rider, Marcus Valentine, Jason Ochoada, Brandon Young, Theresa Nguyen, Sandra J. Kietlinska, Aaron B. Taylor, Burkhard Hoeckendorf, Patrick Rodrigues, Wenwei Lin, Khaled Khairy, Beisi Xu, Anang A. Shelat, Taosheng Chen, Tanja Mittag, Aseem Z. Ansari

{"title":"BRD4 recruitment into HP1 condensates desilences transcription without erasure of repressive chromatin","authors":"Christopher J. Brandon, Sarah Robinson-Thiewes, Mangesh Kaulage, Wojciech Rosikiewicz, Matthew J. Cuneo, Joseph Brett, Jindpreet Kandola, Walter H. Lang, Jonathan Low, Ashraf Mohammed, Adithi Danda, Sam Rider, Marcus Valentine, Jason Ochoada, Brandon Young, Theresa Nguyen, Sandra J. Kietlinska, Aaron B. Taylor, Burkhard Hoeckendorf, Patrick Rodrigues, Wenwei Lin, Khaled Khairy, Beisi Xu, Anang A. Shelat, Taosheng Chen, Tanja Mittag, Aseem Z. Ansari","doi":"10.1038/s41556-026-02044-1","DOIUrl":"10.1038/s41556-026-02044-1","url":null,"abstract":"How genes are desilenced without erasure of repressive chromatin is a poorly understood phenomenon. A dominant mode of repression occurs through methylation of lysine 9 of histone H3 (H3K9me3), a mark that engages heterochromatin protein 1 (HP1) to drive chromatin compaction and transcriptional silencing. The erasure and replacement of this repressive mark with acetyl/acyl groups recruits positive factors such as BRD4/BET to elicit gene transcription. Here we report that, in Friedreich’s ataxia, a synthetic gene regulator (SynGR1/SynTEF1) licenses transcription across repressive chromatin without removal or replacement of H3K9me3 or HP1. By recruiting BRD4/BET into repressive GAA repeats in frataxin (FXN), SynGR1 creates a paradoxical state wherein gene transcription and repressive chromatin coexist. Contrary to convention, we find that BRD4 partitions into phase separated HP1 condensates in vitro and into HP1 puncta in patient-derived cells, thus offering a mechanistic explanation for desilencing transcription without the dispersal of mesoscale repressive chromatin. More broadly, our study highlights the dynamic nature of repressive chromatin and the context dependence of epigenetic marks in regulating gene expression. Brandon, Robinson-Thiewes, Kaulage et al. report that targeted BRD4 recruitment enables transcription through H3K9me3/HP1-marked heterochromatin without erasing repressive marks, identifying condensate partitioning as a mechanism for gene desilencing.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 9","pages":"1846-1856"},"PeriodicalIF":22.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679401","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: Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2–SP1–SAT1 axis 作者更正：癌症相关成纤维细胞衍生的醋酸盐通过ACSS2-SP1-SAT1轴改变多胺代谢，从而促进胰腺癌的发展。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-08-04 DOI: 10.1038/s41556-026-02055-y

Divya Murthy, Kuldeep S. Attri, Surendra K. Shukla, Ravi Thakur, Nina V. Chaika, Chunbo He, Dezhen Wang, Kanupriya Jha, Aneesha Dasgupta, Ryan J. King, Scott E. Mulder, Joshua Souchek, Teklab Gebregiworgis, Vikant Rai, Rohit Patel, Tuo Hu, Sandeep Rana, Sai Sundeep Kollala, Camila Pacheco, Paul M. Grandgenett, Fang Yu, Vikas Kumar, Audrey J. Lazenby, Adrian R. Black, Susanna Ulahannan, Ajay Jain, Barish H. Edil, David L. Klinkebiel, Robert Powers, Amarnath Natarajan, Michael A. Hollingsworth, Kamiya Mehla, Quan Ly, Sarika Chaudhary, Rosa F. Hwang, Kathryn E. Wellen, Pankaj K. Singh

引用次数: 0

Author Correction: Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling 作者更正：结直肠癌类器官中单细胞ERK动力学的量化揭示了EGFR作为致癌MAPK通路信号传导的放大器。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-31 DOI: 10.1038/s41556-026-02050-3

Bas Ponsioen, Jasmin B. Post, Julian R. Buissant des Amorie, Dimitrios Laskaris, Ravian L. van Ineveld, Simone Kersten, Andrea Bertotti, Francesco Sassi, François Sipieter, Benjamin Cappe, Sander Mertens, Ingrid Verlaan-Klink, Sylvia F. Boj, Rob G. J. Vries, Holger Rehmann, Peter Vandenabeele, Franck B. Riquet, Livio Trusolino, Johannes L. Bos, Hugo J. G. Snippert

引用次数: 0

Running towards induced pluripotent stem cells 奔向诱导多能干细胞。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-30 DOI: 10.1038/s41556-026-02029-0

Yanhong Shi

引用次数: 0

The glycolytic enzyme PGAM1 functions as a metabolic–autophagy checkpoint to coordinate growth and stress tolerance 糖酵解酶PGAM1作为代谢自噬检查点来协调生长和应激耐受

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-29 DOI: 10.1038/s41556-026-02034-3

Yi Zhang, Pengwei Zhao, Hangfei Liang, Zhaojie Liu, Shuling Dong, Yingcong Chen, Weijing Yao, Yuting Chen, Liting Yang, Zhonglan Shi, Lei Zhang, Yibin Pan, Fanghong Zheng, Qi Lin, Shichao Wang, Jinheng Pan, Mingzhu Fan, Shan Feng, Cheng Ma, Lifeng Pan, Ying Xing, Fan Yang, Shuiping Liu, Du Feng, Qiming Sun, Guixin Zhu, Cong Yi

{"title":"The glycolytic enzyme PGAM1 functions as a metabolic–autophagy checkpoint to coordinate growth and stress tolerance","authors":"Yi Zhang, Pengwei Zhao, Hangfei Liang, Zhaojie Liu, Shuling Dong, Yingcong Chen, Weijing Yao, Yuting Chen, Liting Yang, Zhonglan Shi, Lei Zhang, Yibin Pan, Fanghong Zheng, Qi Lin, Shichao Wang, Jinheng Pan, Mingzhu Fan, Shan Feng, Cheng Ma, Lifeng Pan, Ying Xing, Fan Yang, Shuiping Liu, Du Feng, Qiming Sun, Guixin Zhu, Cong Yi","doi":"10.1038/s41556-026-02034-3","DOIUrl":"10.1038/s41556-026-02034-3","url":null,"abstract":"Cell survival requires tight coordination between growth-promoting metabolism and cellular quality-control pathways, yet how these processes are integrated remains unclear. Here we identify the conserved glycolytic enzyme PGAM1 as a metabolic-autophagy checkpoint that links glycolysis to autophagy initiation independently of its catalytic activity. Using complementary yeast and mammalian systems we show that PGAM1 functions as a molecular scaffold that recruits phosphatidylinositol 3-kinase complex I to the phagophore assembly site, thereby licensing autophagosome biogenesis. This autophagy-regulatory function is genetically essential, evolutionarily conserved and functionally separable from glycolysis. It is regulated by Atg1/ULK1-mediated phosphorylation that enhances Atg14 binding under starvation. Functionally, PGAM1 coordinates anabolic growth and stress-induced survival to maintain cellular homeostasis. In cancer, PGAM1 upregulation enhances both glycolytic flux and autophagy capacity. Disruption of either function markedly impairs tumour growth, establishing PGAM1 as a homeostatic checkpoint that is hijacked in cancer to drive both proliferation and stress tolerance. Zhang, Zhao, Liang et al. report that, independent of its catalytic function, the glycolytic enzyme PGAM1 acts as a scaffold protein to regulate autophagy activation, thereby modulating cellular homeostasis and stress response.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 9","pages":"1830-1845"},"PeriodicalIF":22.7,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612787","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

Nuclear class 3 PI3K co-activates fasting-specific chromatin remodelling 核3类PI3K共同激活禁食特异性染色质重塑。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-28 DOI: 10.1038/s41556-026-02030-7

Nathaniel F. Henneman, Genki Kawamura, Ying Luo, Catia Oliveira Dias, Jiaqi Su, Arianna Segaloni, Ivan Nemazanyy, Samuel le Cam, Calvin Rodrigues, Nicolas Kuperwasser, Nicolas Cagnard, Karim Hnia, Raphaël Margueron, Dominik Lutter, Takeaki Ozawa, Ganna Panasyuk

{"title":"Nuclear class 3 PI3K co-activates fasting-specific chromatin remodelling","authors":"Nathaniel F. Henneman, Genki Kawamura, Ying Luo, Catia Oliveira Dias, Jiaqi Su, Arianna Segaloni, Ivan Nemazanyy, Samuel le Cam, Calvin Rodrigues, Nicolas Kuperwasser, Nicolas Cagnard, Karim Hnia, Raphaël Margueron, Dominik Lutter, Takeaki Ozawa, Ganna Panasyuk","doi":"10.1038/s41556-026-02030-7","DOIUrl":"10.1038/s41556-026-02030-7","url":null,"abstract":"Transcriptional remodelling during fasting ensures metabolic adaptation and provides health benefits across species. Although several regulators of fasting-induced transcription and chromatin are known, how nutrient levels directly influence RNA polymerase II (RNAPII) and epigenetic writers remains unclear. Here we show that lipid kinase class 3 phosphatidylinositol 3-kinase (PI3K-3), a master regulator of autophagy, also functions on chromatin as a co-activator of epigenetic writers to promote RNAPII transcription. PI3K-3 overlaps with transcriptionally engaged RNAPII phosphorylated at Ser5 and with Setd1a/COMPASS, the complex that deposits the activating H3K4me3 mark. Nuclear PI3K-3 interacts with RNAPII and Setd1a/COMPASS and promotes their chromatin binding. PI3K-3 loss reduces RNAPII-S5p and H3K4me3 at selected genes, whereas PI3K-3 overexpression co-activates p300/CBP and chromatin-targeted PI3K-3 increases H3K4me3. During starvation, PI3K-3 induces autophagy genes and drives fasted liver towards ketogenesis and lipid degradation. These findings link nutrient stress to chromatin-mediated transcriptional activation. Henneman et al. report an unexpected role for class 3 PI3K (PI3K-3) acting as a transcriptional co-activator during fasting. They show that nuclear PI3K-3 co-activates the methyltransferase Set1/COMPASS complex to promote H3K4me3 deposition.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 9","pages":"1875-1889"},"PeriodicalIF":22.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-02030-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605350","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}

引用次数: 0

Cancer stem cells are hyper-responsive sensors of the tumour microenvironment and regulate metastasis dynamics through YAP/TAZ 肿瘤干细胞是肿瘤微环境的高响应传感器，并通过YAP/TAZ调节转移动力学。

IF 22.7 1区生物学

Nature Cell Biology Pub Date : 2026-07-27 DOI: 10.1038/s41556-026-02013-8

Binwu Tang, Jacob Minin, Victoria M. Gonzalez, Zoya Z. Khan, Andrew R. Gaines, Yuval Raviv, Yu-an Yang, Christine P. Carney, Zachary G. Millman, Daniel Grun, Cristiana M. Pineda, Alina Sharma, Dominic Esposito, Hualong Yan, Jing Huang, Andy D. Tran, Michael Kruhlak, Howard H. Yang, Maxwell P. Lee, Lalage M. Wakefield

{"title":"Cancer stem cells are hyper-responsive sensors of the tumour microenvironment and regulate metastasis dynamics through YAP/TAZ","authors":"Binwu Tang, Jacob Minin, Victoria M. Gonzalez, Zoya Z. Khan, Andrew R. Gaines, Yuval Raviv, Yu-an Yang, Christine P. Carney, Zachary G. Millman, Daniel Grun, Cristiana M. Pineda, Alina Sharma, Dominic Esposito, Hualong Yan, Jing Huang, Andy D. Tran, Michael Kruhlak, Howard H. Yang, Maxwell P. Lee, Lalage M. Wakefield","doi":"10.1038/s41556-026-02013-8","DOIUrl":"10.1038/s41556-026-02013-8","url":null,"abstract":"Cancer stem cells (CSCs) drive metastasis and therapy resistance, yet their behaviour within the complex tumour microenvironment remains poorly understood. Here we use a fluorescent reporter that marks CSCs to show that CSCs and their more differentiated progeny display strikingly different population dynamics during metastatic lung colonization in breast cancer models. CSC expansion is rapidly curtailed early in colonization, suggesting a strong negative feedback mechanism acting selectively on this subpopulation. We showed that CSCs are exceptionally sensitive to local microenvironmental cues such as cell crowding and nutrient availability. They respond earlier and more extensively than their differentiated progeny, thereby coupling tumour growth to resource and space availability. Microenvironmental signals converge on the transcriptional regulatory complex YAP/TAZ/TEAD, with CSC sensitivity arising from elevated signal reception and greater chromatin accessibility at TEAD-regulated enhancers. Targeting upstream inputs to this pathway reversed chemotherapy-induced CSC enrichment in lung metastases, suggesting a potential therapeutic strategy. Using a dynamic fluorescent reporter, Tang et al. demonstrate that cancer stem cells are hyper-responsive to microenvironmental cues, which they sense and adapt to through YAP/TAZ signalling, thereby playing an essential role in breast cancer lung metastasis.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 8","pages":"1728-1741"},"PeriodicalIF":22.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-026-02013-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605373","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}

引用次数: 0