Nature genetics最新文献

KDM4C inhibition blocks tumor growth in basal breast cancer by promoting cathepsin L-mediated histone H3 cleavage KDM4C抑制通过促进组织蛋白酶l介导的组蛋白H3切割来阻止基底乳腺癌的肿瘤生长

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-06-02 DOI: 10.1038/s41588-025-02197-z

Zheqi Li, Guillermo Peluffo, Laura E. Stevens, Xintao Qiu, Marco Seehawer, Amatullah Tawawalla, Xiao-Yun Huang, Shawn B. Egri, Shaunak Raval, Maeve McFadden, Clive S. D’Santos, Eva Papachristou, Natalie L. Kingston, Jun Nishida, Kyle E. Evans, Ji-Heui Seo, Kendell Clement, Daniel Temko, Muhammad Ekram, Rong Li, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Anton Simeonov, Stephen C. Kales, Ganesha Rai, Madhu Lal-Nag, David J. Maloney, Ajit Jadhav, Franziska Michor, Alex Meissner, Justin M. Balko, Jason S. Carroll, Matthew L. Freedman, Jacob D. Jaffe, Malvina Papanastasiou, Henry W. Long, Kornelia Polyak

{"title":"KDM4C inhibition blocks tumor growth in basal breast cancer by promoting cathepsin L-mediated histone H3 cleavage","authors":"Zheqi Li, Guillermo Peluffo, Laura E. Stevens, Xintao Qiu, Marco Seehawer, Amatullah Tawawalla, Xiao-Yun Huang, Shawn B. Egri, Shaunak Raval, Maeve McFadden, Clive S. D’Santos, Eva Papachristou, Natalie L. Kingston, Jun Nishida, Kyle E. Evans, Ji-Heui Seo, Kendell Clement, Daniel Temko, Muhammad Ekram, Rong Li, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Anton Simeonov, Stephen C. Kales, Ganesha Rai, Madhu Lal-Nag, David J. Maloney, Ajit Jadhav, Franziska Michor, Alex Meissner, Justin M. Balko, Jason S. Carroll, Matthew L. Freedman, Jacob D. Jaffe, Malvina Papanastasiou, Henry W. Long, Kornelia Polyak","doi":"10.1038/s41588-025-02197-z","DOIUrl":"https://doi.org/10.1038/s41588-025-02197-z","url":null,"abstract":"Basal breast cancer is a subtype with a poor prognosis in need of more effective therapeutic approaches. Here we describe a unique role for the KDM4C histone lysine demethylase in KDM4C-amplified basal breast cancers, where KDM4C inhibition reshapes chromatin and transcriptomic landscapes without substantial alterations of its canonical substrates, trimethylated histone H3 lysine 9 (H3K9me3) and lysine 36 (H3K36me3). Rather, KDM4C loss causes proteolytic cleavage of histone H3 mediated by cathepsin L (CTSL), resulting in decreased glutamate–cysteine ligase expression and increased reactive oxygen species. CTSL is recruited to the chromatin by the grainyhead-like 2 (GRHL2) transcription factor that is methylated at lysine 453 following KDM4C inhibition, triggering CTSL histone clipping activity. Deletion of CTSL rescued KDM4-loss-mediated tumor suppression. Our study reveals a function for KDM4C that connects cellular redox regulation and chromatin remodeling.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"51 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144193046","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

Engineering next-generation microfluidic technologies for single-cell phenomics 为单细胞表型组学设计下一代微流体技术

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-06-02 DOI: 10.1038/s41588-025-02198-y

Camille L. G. Lambert, Guido van Mierlo, Johannes J. Bues, Orane J. Guillaume-Gentil, Bart Deplancke

{"title":"Engineering next-generation microfluidic technologies for single-cell phenomics","authors":"Camille L. G. Lambert, Guido van Mierlo, Johannes J. Bues, Orane J. Guillaume-Gentil, Bart Deplancke","doi":"10.1038/s41588-025-02198-y","DOIUrl":"https://doi.org/10.1038/s41588-025-02198-y","url":null,"abstract":"The completion of the Human Genome Project catalyzed the development of ‘omics’ technologies, enabling the detailed exploration of biological systems at an unprecedented molecular scale. Microfluidics has transformed the omics toolbox by facilitating large-scale, high-throughput and highly accurate measurements of DNA and RNA, driving the transition from bulk to single-cell analyses. This transition has ushered in a new era, moving beyond a gene- and protein-centric perspective toward a holistic understanding of cellular phenotypes. This emerging ‘single-cell phenomics era’ integrates diverse omics datasets with spatial, morphological and temporal phenotypes to provide a comprehensive perspective on cellular function. This Review highlights how microfluidics addressed key challenges in the transition to single-cell omics and explores how lessons learned from these efforts will propel the single-cell phenomics revolution. Furthermore, we discuss emerging opportunities in which integrative single-cell phenomics could serve as a foundation for transformative discoveries in biology.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"5 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144193048","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

Towards trustworthiness of precision medicine research for people with disabilities 迈向残疾人精准医学研究的可信赖性

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-06-02 DOI: 10.1038/s41588-025-02195-1

Alejandra Aguirre, Sandra Soo-Jin Lee, Shawneequa Callier, Paul Spicer, Maya Sabatello

引用次数: 0

Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters 系统发育推断揭示了循环肿瘤细胞群的克隆异质性

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-06-02 DOI: 10.1038/s41588-025-02205-2

David Gremmelspacher, Johannes Gawron, Barbara M. Szczerba, Katharina Jahn, Francesc Castro-Giner, Jack Kuipers, Jochen Singer, Francesco Marass, Ana Gvozdenovic, Selina Budinjas, Heike Pueschel, Cyrill A. Rentsch, Alfred Zippelius, Viola Heinzelmann-Schwarz, Christian Kurzeder, Walter Paul Weber, Christoph Rochlitz, Marcus Vetter, Niko Beerenwinkel, Nicola Aceto

引用次数: 0

Longitudinal and multisite sampling reveals mutational and copy number evolution in tumors during metastatic dissemination 纵向和多点采样揭示肿瘤在转移传播过程中的突变和拷贝数进化

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-06-02 DOI: 10.1038/s41588-025-02204-3

Karena Zhao, Joris Vos, Stanley Lam, Lillian A. Boe, Daniel Muldoon, Catherine Y. Han, Cristina Valero, Mark Lee, Conall Fitzgerald, Andrew S. Lee, Manu Prasad, Swati Jain, Xinzhu Deng, Timothy A. Chan, Michael F. Berger, Chaitanya Bandlamudi, Xi Kathy Zhou, Luc G. T. Morris

{"title":"Longitudinal and multisite sampling reveals mutational and copy number evolution in tumors during metastatic dissemination","authors":"Karena Zhao, Joris Vos, Stanley Lam, Lillian A. Boe, Daniel Muldoon, Catherine Y. Han, Cristina Valero, Mark Lee, Conall Fitzgerald, Andrew S. Lee, Manu Prasad, Swati Jain, Xinzhu Deng, Timothy A. Chan, Michael F. Berger, Chaitanya Bandlamudi, Xi Kathy Zhou, Luc G. T. Morris","doi":"10.1038/s41588-025-02204-3","DOIUrl":"https://doi.org/10.1038/s41588-025-02204-3","url":null,"abstract":"To understand genetic evolution in cancer during metastasis, we analyzed genomic profiles of 3,732 cancer patients in whom several tumor sites were longitudinally biopsied. During distant metastasis, tumors were observed to accumulate copy number alterations (CNAs) to a much greater degree than mutations. In particular, the development of whole genome duplication was a common event during metastasis, emerging de novo in 28% of patients. Loss of 9p (including CDKN2A) developed during metastasis in 11% of patients. To a lesser degree, mutations and allelic loss in human leukocyte antigen class I and other genes associated with antigen presentation also emerged. Increasing CNA, but not increasing mutational load, was associated with immune evasion in patients treated with immunotherapy. Taken together, these data suggest that CNA, rather than mutational accumulation, is enriched during cancer metastasis, perhaps due to a more favorable balance of enhanced cellular fitness versus immunogenicity.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"3 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144193047","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

A simple genomic score to predict progression of multiple myeloma 一个简单的基因组评分预测多发性骨髓瘤的进展

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-05-30 DOI: 10.1038/s41588-025-02199-x

引用次数: 0

Realizing the promise of genome-wide association studies for effector gene prediction 实现效应基因预测全基因组关联研究的前景

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-05-29 DOI: 10.1038/s41588-025-02210-5

Maria C. Costanzo, Laura W. Harris, Yue Ji, Aoife McMahon, Noël P. Burtt, Jason Flannick

引用次数: 0

Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as neurodevelopmental disorder genes R-loop形成区分析确定RNU2-2和RNU5B-1为神经发育障碍基因

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-05-29 DOI: 10.1038/s41588-025-02209-y

Adam Jackson, Nishi Thaker, Alexander Blakes, Gillian Rice, Sam Griffiths-Jones, Meena Balasubramanian, Jennifer Campbell, Nora Shannon, Jungmin Choi, Juhyeon Hong, David Hunt, Anna de Burca, Soo Yeon Kim, Taekeun Kim, Seungbok Lee, Melody Redman, Rocio Rius, Cas Simons, Tiong Yang Tan, Jamie Ellingford, Raymond T. O’Keefe, Jong Hee Chae, Siddharth Banka

引用次数: 0

Author Correction: Distinct dynamics and functions of H2AK119ub1 and H3K27me3 in mouse preimplantation embryos 作者更正：H2AK119ub1和H3K27me3在小鼠植入前胚胎中的不同动态和功能

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-05-28 DOI: 10.1038/s41588-025-02211-4

Zhiyuan Chen, Mohamed Nadhir Djekidel, Yi Zhang

引用次数: 0

Genome synteny reveals hidden enhancer conservation 基因组合成揭示了隐藏的增强子保护

IF 30.8 1区生物学

Nature genetics Pub Date : 2025-05-27 DOI: 10.1038/s41588-025-02194-2

Alex de Mendoza

引用次数: 0