Nature genetics最新文献_第4页

An atypical NLR pair TdCNL1/TdCNL5 from wild emmer confers powdery mildew resistance in wheat 来自野生二聚体的非典型NLR对TdCNL1/TdCNL5赋予小麦白粉病抗性

IF 31.7 1区生物学

Nature genetics Pub Date : 2025-06-09 DOI: 10.1038/s41588-025-02208-z

Keyu Zhu, Miaomiao Li, Lingli Dong, Huaizhi Zhang, Deyun Zhang, Ping Lu, Qiuhong Wu, Jingzhong Xie, Yongxing Chen, Guanghao Guo, Panpan Zhang, Beibei Li, Wenling Li, Lei Dong, Yikun Hou, Yijun Yang, Dan Qiu, Gaojie Wang, Baoge Huang, Xuejia Cui, Hongkui Fu, Chengguo Yuan, Tzion Fahima, Eviatar Nevo, Hongjie Li, Junkang Rong, Wei Hua, Zhiyong Liu

{"title":"An atypical NLR pair TdCNL1/TdCNL5 from wild emmer confers powdery mildew resistance in wheat","authors":"Keyu Zhu, Miaomiao Li, Lingli Dong, Huaizhi Zhang, Deyun Zhang, Ping Lu, Qiuhong Wu, Jingzhong Xie, Yongxing Chen, Guanghao Guo, Panpan Zhang, Beibei Li, Wenling Li, Lei Dong, Yikun Hou, Yijun Yang, Dan Qiu, Gaojie Wang, Baoge Huang, Xuejia Cui, Hongkui Fu, Chengguo Yuan, Tzion Fahima, Eviatar Nevo, Hongjie Li, Junkang Rong, Wei Hua, Zhiyong Liu","doi":"10.1038/s41588-025-02208-z","DOIUrl":"10.1038/s41588-025-02208-z","url":null,"abstract":"Resistance to wheat powdery mildew is commonly mediated by individual resistance proteins, most of which encode nucleotide-binding leucine-rich repeat (NLR) receptors. Here we report that the powdery mildew resistance gene MLIW170/PM26 in wild emmer and bread wheat derivatives is determined by a genetically linked atypical NLR pair TdCNL1/TdCNL5. Map-based cloning and PacBio HiFi long-read sequencing revealed that TdCNL1 encodes an atypical coiled-coil-domain-containing NLR protein (CNL) fused with a new potassium-dependent sodium-calcium exchanger integrated domain, whereas TdCNL5 encodes a canonical CNL protein. Mutagenesis and virus-induced gene silencing experiments indicated that both TdCNL1 and TdCNL5 are essential for powdery mildew resistance. Transgenic plants with TdCNL1 alone or TdCNL1/TdCNL5 together show resistance, whereas Fielder with TdCNL5 alone was susceptible. Geographically, MLIW170/PM26 occurs in a few Southern populations of wild emmer wheat. Our study highlights an atypical NLR pair coordinately regulating powdery mildew resistance and provides a diversified resistance gene resource for wheat improvement. The powdery mildew resistance of the MLIW170/PM26 locus, which originated from wild emmer wheat, is determined by a genetically linked atypical NLR gene pair, TdCNL1 and TdCNL5, with TdCNL1 encoding an atypical nucleotide-binding leucine-rich repeat protein integrating a potassium-dependent sodium-calcium exchanger domain.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1553-1562"},"PeriodicalIF":31.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237780","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

KDM4C shields breast cancer from the histone scissor cathepsin L KDM4C保护乳腺癌免受组蛋白剪刀组织蛋白酶L的侵害

IF 31.7 1区生物学

Nature genetics Pub Date : 2025-06-05 DOI: 10.1038/s41588-025-02200-7

引用次数: 0

High-definition spatial transcriptomic profiling of immune cell populations in colorectal cancer 结直肠癌免疫细胞群的高清晰度空间转录组学分析

IF 31.7 1区生物学

Nature genetics Pub Date : 2025-06-05 DOI: 10.1038/s41588-025-02193-3

Michelli Faria de Oliveira, Juan Pablo Romero, Meii Chung, Stephen R. Williams, Andrew D. Gottscho, Anushka Gupta, Susan E. Pilipauskas, Seayar Mohabbat, Nandhini Raman, David J. Sukovich, David M. Patterson, Visium HD Development Team, Sarah E. B. Taylor

{"title":"High-definition spatial transcriptomic profiling of immune cell populations in colorectal cancer","authors":"Michelli Faria de Oliveira, Juan Pablo Romero, Meii Chung, Stephen R. Williams, Andrew D. Gottscho, Anushka Gupta, Susan E. Pilipauskas, Seayar Mohabbat, Nandhini Raman, David J. Sukovich, David M. Patterson, Visium HD Development Team, Sarah E. B. Taylor","doi":"10.1038/s41588-025-02193-3","DOIUrl":"10.1038/s41588-025-02193-3","url":null,"abstract":"A comprehensive understanding of cellular behavior and response to the tumor microenvironment (TME) in colorectal cancer (CRC) remains elusive. Here, we introduce the high-definition Visium spatial transcriptomic technology (Visium HD) and investigate formalin-fixed paraffin-embedded human CRC samples (n = 5). We demonstrate the high sensitivity, single-cell-scale resolution and spatial accuracy of Visium HD, generating a highly refined whole-transcriptome spatial profile of CRC samples. We identify transcriptomically distinct macrophage subpopulations in different spatial niches with potential pro-tumor and anti-tumor functions via interactions with tumor and T cells. In situ gene expression analysis validates our findings and localizes a clonally expanded T cell population close to macrophages with anti-tumor features. Our study demonstrates the power of high-resolution spatial technologies to understand cellular interactions in the TME and paves the way for larger studies that will unravel mechanisms and biomarkers of CRC biology, improving diagnosis and disease management strategies. High-resolution, spatial transcriptomic analysis of colorectal cancers using matched sequencing- and imaging-based methods characterizes immune cells and their interactions with the tumor microenvironment.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1512-1523"},"PeriodicalIF":31.7,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02193-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218899","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

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 31.7 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":"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. KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1463-1477"},"PeriodicalIF":31.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02197-z.pdf","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":"OA","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 31.7 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":"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. Research is moving from a gene- and protein-centric view toward a holistic understanding of cellular phenotypes. This Review discusses the technological microfluidics challenges that must be addressed to realize integrative single-cell phenomics.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1344-1356"},"PeriodicalIF":31.7,"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 31.7 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 31.7 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

{"title":"Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters","authors":"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","doi":"10.1038/s41588-025-02205-2","DOIUrl":"10.1038/s41588-025-02205-2","url":null,"abstract":"Circulating tumor cell (CTC) clusters are highly efficient metastatic seeds in various cancers. Yet, their genetic heterogeneity and clonal architecture is poorly characterized. Using whole-exome sequencing coupled with phylogenetic inference from CTC clusters of patients with breast and prostate cancer, as well as mouse cancer models alongside barcode-mediated clonal tracking in vivo, we demonstrate oligoclonal composition of individual CTC clusters. These results improve our understanding of metastasis-relevant clonal dynamics. Phylogenetic analyses in patients with cancer and xenograft models highlight heterogeneity within individual CTC clusters, providing insights into clonal dynamics during metastasis.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1357-1361"},"PeriodicalIF":31.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02205-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144193120","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

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 31.7 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":"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. A pan-cancer analysis of genomic data from matched primary and metastatic tumors from 3,732 patients shows that increased genomic complexity and alterations that facilitate immune evasion are associated with disease progression.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 6","pages":"1504-1511"},"PeriodicalIF":31.7,"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 31.7 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