Nature Methods最新文献_第3页

Perturb-tracing enables high-content screening of multi-scale 3D genome regulators. 摄动追踪能够对多尺度3D基因组调控因子进行高含量筛选。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-04-10 DOI: 10.1038/s41592-025-02652-z

Yubao Cheng, Mengwei Hu, Bing Yang, Tyler B Jensen, Yuan Zhang, Tianqi Yang, Ruihuan Yu, Zhaoxia Ma, Jonathan S D Radda, Shengyan Jin, Chongzhi Zang, Siyuan Wang

{"title":"Perturb-tracing enables high-content screening of multi-scale 3D genome regulators.","authors":"Yubao Cheng, Mengwei Hu, Bing Yang, Tyler B Jensen, Yuan Zhang, Tianqi Yang, Ruihuan Yu, Zhaoxia Ma, Jonathan S D Radda, Shengyan Jin, Chongzhi Zang, Siyuan Wang","doi":"10.1038/s41592-025-02652-z","DOIUrl":"10.1038/s41592-025-02652-z","url":null,"abstract":"Three-dimensional (3D) genome organization becomes altered during development, aging and disease, but the factors regulating chromatin topology are incompletely understood and currently no technology can efficiently screen for new regulators of multi-scale chromatin organization. Here, we developed an image-based high-content screening platform (Perturb-tracing) that combines pooled CRISPR screens, a cellular barcode readout method (BARC-FISH) and chromatin tracing. We performed a loss-of-function screen in human cells, and visualized alterations to their 3D chromatin folding conformations, alongside perturbation-paired barcode readout in the same single cells. We discovered tens of new regulators of chromatin folding at different length scales, ranging from chromatin domains and compartments to chromosome territory. A subset of the regulators exhibited 3D genome effects associated with loop extrusion and A-B compartmentalization mechanisms, while others were largely unrelated to these known 3D genome mechanisms. Finally, we identified new regulators of nuclear architectures and found a functional link between chromatin compaction and nuclear shape. Altogether, our method enables scalable, high-content identification of chromatin and nuclear topology regulators that will stimulate new insights into the 3D genome.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"950-961"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064297","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

CarboTag: a modular approach for live and functional imaging of plant cell walls. CarboTag：一种模块化方法，用于植物细胞壁的活性和功能成像。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02677-4

Maarten Besten, Milan Hendriksz, Lucile Michels, Bénédicte Charrier, Elwira Smakowska-Luzan, Dolf Weijers, Jan Willem Borst, Joris Sprakel

引用次数: 0

AI carves out a niche in ecology and conservation research. 人工智能在生态学和自然保护研究中占有一席之地。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02682-7

Virginia Gewin

引用次数: 0

Tri-omic single-cell mapping of the 3D epigenome and transcriptome in whole mouse brains throughout the lifespan. 整个小鼠大脑中三维表观基因组和转录组的三组单细胞图谱。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-04-29 DOI: 10.1038/s41592-025-02658-7

Haoxi Chai, Xingyu Huang, Guangzhou Xiong, Jiaxiang Huang, Katarzyna Karolina Pels, Lingyun Meng, Jin Han, Dongmei Tang, Guanjing Pan, Liang Deng, Qin Xiao, Xiaotao Wang, Meng Zhang, Krzysztof Banecki, Dariusz Plewczynski, Chia-Lin Wei, Yijun Ruan

{"title":"Tri-omic single-cell mapping of the 3D epigenome and transcriptome in whole mouse brains throughout the lifespan.","authors":"Haoxi Chai, Xingyu Huang, Guangzhou Xiong, Jiaxiang Huang, Katarzyna Karolina Pels, Lingyun Meng, Jin Han, Dongmei Tang, Guanjing Pan, Liang Deng, Qin Xiao, Xiaotao Wang, Meng Zhang, Krzysztof Banecki, Dariusz Plewczynski, Chia-Lin Wei, Yijun Ruan","doi":"10.1038/s41592-025-02658-7","DOIUrl":"10.1038/s41592-025-02658-7","url":null,"abstract":"Exploring the genomic basis of transcriptional programs has been a long-standing research focus. Here we report a single-cell method, ChAIR, to map chromatin accessibility, chromatin interactions and RNA expression simultaneously. After validating in cultured cells, we applied ChAIR to whole mouse brains and delineated the concerted dynamics of epigenome, three-dimensional (3D) genome and transcriptome during maturation and aging. In particular, gene-centric chromatin interactions and open chromatin states provided 3D epigenomic mechanism underlying cell-type-specific transcription and revealed spatially resolved specificity. Importantly, the composition of short-range and ultralong chromatin contacts in individual cells is remarkably correlated with transcriptional activity, open chromatin state and genome folding density. This genomic property, along with associated cellular properties, differs in neurons and non-neuronal cells across different anatomic regions throughout the lifespan, implying divergent nuclear mechano-genomic mechanisms at play in brain cells. Our results demonstrate ChAIR's robustness in revealing single-cell 3D epigenomic states of cell-type-specific transcription in complex tissues.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"994-1007"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982105","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

TEMI: tissue-expansion mass-spectrometry imaging. TEMI：组织膨胀质谱成像。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-04-22 DOI: 10.1038/s41592-025-02664-9

Hua Zhang, Lang Ding, Amy Hu, Xudong Shi, Penghsuan Huang, Haiyan Lu, Paul W Tillberg, Meng C Wang, Lingjun Li

引用次数: 0

Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering. 利用超灵敏重加权可见受激拉曼散射技术进行细胞代谢的无标记纳米观察。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-01-16 DOI: 10.1038/s41592-024-02575-1

Haonan Lin, Scott Seitz, Yuying Tan, Jean-Baptiste Lugagne, Le Wang, Guangrui Ding, Hongjian He, Tyler J Rauwolf, Mary J Dunlop, John H Connor, John A Porco, Lei Tian, Ji-Xin Cheng

{"title":"Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering.","authors":"Haonan Lin, Scott Seitz, Yuying Tan, Jean-Baptiste Lugagne, Le Wang, Guangrui Ding, Hongjian He, Tyler J Rauwolf, Mary J Dunlop, John H Connor, John A Porco, Lei Tian, Ji-Xin Cheng","doi":"10.1038/s41592-024-02575-1","DOIUrl":"10.1038/s41592-024-02575-1","url":null,"abstract":"Super-resolution imaging of cell metabolism is hindered by the incompatibility of small metabolites with fluorescent dyes and the limited resolution of imaging mass spectrometry. We present ultrasensitive reweighted visible stimulated Raman scattering (URV-SRS), a label-free vibrational imaging technique for multiplexed nanoscopy of intracellular metabolites. We developed a visible SRS microscope with extensive pulse chirping to improve the detection limit to ~4,000 molecules and introduced a self-supervised multi-agent denoiser to suppress non-independent noise in SRS by over 7.2 dB, resulting in a 50-fold sensitivity enhancement over near-infrared SRS. Leveraging the enhanced sensitivity, we employed Fourier reweighting to amplify sub-100-nm spatial frequencies that were previously overwhelmed by noise. Validated by Fourier ring correlation, we achieved a lateral resolution of 86 nm in cell imaging. We visualized the reprogramming of metabolic nanostructures associated with virus replication in host cells and subcellular fatty acid synthesis in engineered bacteria, demonstrating its capability towards nanoscopic spatial metabolomics.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":"1040-1050"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008708","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

Scaling a foundational protein language model to 100 billion parameters. 将基础蛋白质语言模型扩展到1000亿个参数。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02637-y

引用次数: 0

Tracking gene transfer using RNA tools. 利用RNA工具追踪基因转移。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02710-6

Lei Tang

引用次数: 0

Fast-adaptive super-resolution lattice light-sheet microscopy for rapid, long-term, near-isotropic subcellular imaging. 用于快速、长期、近各向同性亚细胞成像的快速自适应超分辨率晶格光片显微镜。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 Epub Date: 2025-04-29 DOI: 10.1038/s41592-025-02678-3

Chang Qiao, Ziwei Li, Zongfa Wang, Yuhuan Lin, Chong Liu, Siwei Zhang, Yong Liu, Yun Feng, Xiaoyu Yang, Wenfeng Fu, Xue Dong, Jiabao Guo, Wencong Xu, Xinyu Wang, Tao Jiang, Quan Meng, Qinghua Wang, Qionghai Dai, Dong Li

{"title":"Fast-adaptive super-resolution lattice light-sheet microscopy for rapid, long-term, near-isotropic subcellular imaging.","authors":"Chang Qiao, Ziwei Li, Zongfa Wang, Yuhuan Lin, Chong Liu, Siwei Zhang, Yong Liu, Yun Feng, Xiaoyu Yang, Wenfeng Fu, Xue Dong, Jiabao Guo, Wencong Xu, Xinyu Wang, Tao Jiang, Quan Meng, Qinghua Wang, Qionghai Dai, Dong Li","doi":"10.1038/s41592-025-02678-3","DOIUrl":"https://doi.org/10.1038/s41592-025-02678-3","url":null,"abstract":"Lattice light-sheet microscopy provides a crucial observation window into intra- and intercellular physiology of living specimens but at the diffraction-limited resolution or anisotropic super-resolution with structured illumination. Here we present meta-learning-empowered reflective lattice light-sheet virtual structured illumination microscopy (Meta-rLLS-VSIM), which upgrades lattice light-sheet microscopy to a near-isotropic super resolution of ~120 nm laterally and ~160 nm axially without modifications of the core optical system or loss of other live-cell imaging metrics. Moreover, we devised an adaptive online training approach by synergizing the front-end imaging system and back-end meta-learning framework, which alleviated the demand for training data by tenfold and reduced the total time for data acquisition and model training down to tens of seconds. We demonstrate the versatile functionalities of Meta-rLLS-VSIM by imaging a variety of bioprocesses with ultrahigh spatiotemporal resolution for hundreds of multicolor volumes, delineating the nanoscale distributions, dynamics and interaction patterns of multiple organelles in embryos and eukaryotic cells.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 5","pages":"1059-1069"},"PeriodicalIF":36.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019501","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 20-year journey on the invention of vibrational photothermal microscopy. 振动光热显微镜发明的20年历程。

IF 36.1 1区生物学

Nature Methods Pub Date : 2025-05-01 DOI: 10.1038/s41592-025-02619-0

Ji-Xin Cheng

引用次数: 0