Nature Methods最新文献_第2页

A self-organized pencil beam that can be used for fast volumetric imaging. 一种可用于快速体积成像的自组织铅笔束。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-27 DOI: 10.1038/s41592-026-03094-x

引用次数: 0

Spatial 5mC-seq profiling of embryos and decidua after implantation in mammals. 哺乳动物着床后胚胎和蜕膜的空间5mC-seq分析。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-27 DOI: 10.1038/s41592-026-03079-w

Xun Shan, Yimin Tang, Jinzhou Hu, Mingyuan Bian, Xuelong Yao, Lei Gao, Jiang Liu

{"title":"Spatial 5mC-seq profiling of embryos and decidua after implantation in mammals.","authors":"Xun Shan, Yimin Tang, Jinzhou Hu, Mingyuan Bian, Xuelong Yao, Lei Gao, Jiang Liu","doi":"10.1038/s41592-026-03079-w","DOIUrl":"https://doi.org/10.1038/s41592-026-03079-w","url":null,"abstract":"DNA methylation is vital for development and diseases, yet no spatial DNA methylation profiling technology has been reported. Here we developed spatial 5mC-seq (SmC-seq), a microfluidic-based method providing unbiased genome-wide methylome at near single-cell resolution. Applying SmC-seq to mouse post-implantation development revealed a clear spatial heterogenous pattern of DNA methylation in inner cell mass-derived tissues. We identified a two-layer organization in the E8.5 ectoplacental cone with distinct methylation and proliferation states. Unexpectedly, a portion of maternal tissue with low DNA methylation level, enriched for nutrient-supplier progenitors, is observed in the middle region of decidua post-implantation. The hypomethylated regions in the nutrient-supplier progenitor cluster are associated with cell proliferation. Notably, the genes associated with hypomethylated regions in mature nutrient-supplier cluster are enriched in exocytosis and nutrient synthesis, linked to nutrient provision for embryogenesis before placental function. In summary, SmC-seq enables spatial DNA methylation mapping, advancing our understanding of biological events.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":32.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777048","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

Direct RNA sequencing and signal alignment reveal RNA structure ensembles in a eukaryotic cell. 直接RNA测序和信号比对揭示了真核细胞中的RNA结构集合体。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-24 DOI: 10.1038/s41592-026-03069-y

Jiaxu Wang, Jian Han, Wen Ting Tan, Anthony Youzhi Cheng, Jong Ghut Ashley Aw, Yue Wang, Guisheng Zeng, Niranjan Nagarajan, Yue Wan

{"title":"Direct RNA sequencing and signal alignment reveal RNA structure ensembles in a eukaryotic cell.","authors":"Jiaxu Wang, Jian Han, Wen Ting Tan, Anthony Youzhi Cheng, Jong Ghut Ashley Aw, Yue Wang, Guisheng Zeng, Niranjan Nagarajan, Yue Wan","doi":"10.1038/s41592-026-03069-y","DOIUrl":"https://doi.org/10.1038/s41592-026-03069-y","url":null,"abstract":"The extent to which an RNA folds into structure ensembles and how different structures in the ensemble regulate eukaryotic gene expression is not fully understood. Here, we coupled chemical probing with direct RNA sequencing to identify structure modifications along a single RNA molecule (sm-PORE-cupine). We used direct signal alignment in addition to base mapping to increase the percentage of mappable sequences and showed that Bernoulli mixture model clustering can separate structure ensembles accurately. We applied sm-PORE-cupine to identify isoform-specific structure ensembles along the SARS-CoV-2 genome and structure ensembles in the Candida albicans transcriptome. We observed that RNAs are more structurally homogeneous in vitro, at higher temperatures and in the 3' untranslated regions of C. albicans. Structure ensembles are associated with changes in translation efficiency and decay in C. albicans, and we validated translation changes using reporter assays. sm-PORE-cupine expands the existing toolbox for studying RNA structure and function in diverse transcriptomes.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":32.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776983","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

PinkyCaMP: an mScarlet-based calcium sensor with enhanced brightness, photostability and multiplexing capabilities. PinkyCaMP：一种基于mscarlet的钙传感器，具有增强的亮度、光稳定性和多路复用能力。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-24 DOI: 10.1038/s41592-026-03065-2

Ryan Fink, Shosei Imai, Nala Gockel, German Lauer, Kim Renken, Jonas Wietek, Paul J Lamothe-Molina, Falko Fuhrmann, Manuel Mittag, Tim Ziebarth, Annika Canziani, Martin Kubitschke, Vivien Kistmacher, Anny Kretschmer, Eva Sebastian, Jana Ottens, Dietmar Schmitz, Takuya Terai, Jan Gründemann, Sami I Hassan, Tommaso Patriarchi, Andreas Reiner, Martin Fuhrmann, Robert E Campbell, Olivia Andrea Masseck

{"title":"PinkyCaMP: an mScarlet-based calcium sensor with enhanced brightness, photostability and multiplexing capabilities.","authors":"Ryan Fink, Shosei Imai, Nala Gockel, German Lauer, Kim Renken, Jonas Wietek, Paul J Lamothe-Molina, Falko Fuhrmann, Manuel Mittag, Tim Ziebarth, Annika Canziani, Martin Kubitschke, Vivien Kistmacher, Anny Kretschmer, Eva Sebastian, Jana Ottens, Dietmar Schmitz, Takuya Terai, Jan Gründemann, Sami I Hassan, Tommaso Patriarchi, Andreas Reiner, Martin Fuhrmann, Robert E Campbell, Olivia Andrea Masseck","doi":"10.1038/s41592-026-03065-2","DOIUrl":"https://doi.org/10.1038/s41592-026-03065-2","url":null,"abstract":"Genetically encoded calcium (Ca2+) indicators (GECIs) are essential tools for monitoring neuronal activity, but the performance of red fluorescent GECIs has remained limited. In particular, many red indicators are relatively dim, produce low signal-to-noise ratios and can undergo unwanted photoswitching when exposed to blue light, restricting their use in all-optical experiments that combine imaging with optogenetics or multicolor imaging. Here we show the development of PinkyCaMP, a Ca2+ sensor based on the bright red fluorescent protein mScarlet. PinkyCaMP exhibits markedly improved brightness, photostability and signal-to-noise ratio compared to existing red GECIs, while remaining fully compatible with blue-light-based optogenetic and dual-color imaging approaches. PinkyCaMP is well-tolerated by neurons, showing no detectable toxicity or aggregation, both in vitro and in vivo. PinkyCaMP enables a broad spectrum of imaging modalities, including single-photon methods, such as fiber photometry, widefield imaging and miniature microscopy imaging, as well as two-photon imaging in awake mice.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":32.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777030","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

Systematically decoding pathological morphologies and molecular profiles with unified multimodal embedding. 用统一的多模态嵌入系统地解码病理形态和分子图谱。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-24 DOI: 10.1038/s41592-026-03070-5

Peng Zhang, Chaofei Gao, Kui Hua, Zhuoyu Zhang, Shao Li

引用次数: 0

Synthetic multicolor antigen-stabilizable nanobody platform for intersectional labeling and functional imaging. 用于交叉标记和功能成像的合成多色抗原稳定纳米体平台。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-22 DOI: 10.1038/s41592-026-03056-3

Natalia V Barykina, Erin M Carey, Olena S Oliinyk, Juliana M Mendonça-Gomes, Sofia de Oliveira, Axel Nimmerjahn, Vladislav V Verkhusha

{"title":"Synthetic multicolor antigen-stabilizable nanobody platform for intersectional labeling and functional imaging.","authors":"Natalia V Barykina, Erin M Carey, Olena S Oliinyk, Juliana M Mendonça-Gomes, Sofia de Oliveira, Axel Nimmerjahn, Vladislav V Verkhusha","doi":"10.1038/s41592-026-03056-3","DOIUrl":"10.1038/s41592-026-03056-3","url":null,"abstract":"We present a synthetic tool kit of antigen-stabilizable fluorescent nanobodies (VIS-Fbs) spanning the entire visible spectrum from 450 nm to 660 nm. By engineering over 20 fluorescent proteins (FPs) and biosensors into 8 nanobodies, we established a generalizable design of VIS-Fbs, which fluoresce brightly only upon binding to cognate antigens. Our synthetic approach includes constitutive, photoactivatable and photoswitchable FPs, as well as intensiometric FP-based biosensors. VIS-Fbs carrying biosensors enable simultaneous monitoring of two metabolites at confined locations, while FP-based VIS-Fbs targeting biosensors allow ratiometric functional imaging in mouse brain. We further used VIS-Fbs to track endogenous β-catenin dynamics in zebrafish embryos during normal development and under Wnt-β-catenin signaling modulation. VIS-Fbs provide background-free visualization of intracellular proteins, multicolor detection of multiple antigens and selective targeting of defined cell populations and compartments. This synthetic biology-driven platform enables precise studies of protein dynamics, cellular processes and complex biological systems with high specificity and minimal background.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":32.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776980","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

GloBIAS: strengthening the foundations of bioimage analysis. 加强生物图像分析的基础。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-22 DOI: 10.1038/s41592-026-03060-7

Agustin A Corbat, Christa G Walther, Laura R de la Ballina, Nicholas D Condon, Alessandro A Felder, Martin Schätz, Bettina Schmerl, Ko Sugawara, Clara Prats, Anna Klemm, Kota Miura, Paula Sampaio, Christian Tischer, Florian Levet, Rocco D'Antuono, Beth A Cimini, Robert Haase

引用次数: 0

NirFAP680: a highly bright and stable large Stokes shift near-infrared fluorogen-activating protein. NirFAP680：一种高亮度和稳定的大斯托克斯位移近红外氟激活蛋白。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-21 DOI: 10.1038/s41592-026-03061-6

Zhengda Chen, Li Jiang, Xiaoyu Liu, Yajie Shi, Yang Liu, Ling Jiang, Jiaxin Li, Xinyi Huang, Siyu Zhou, Bingkun Bao, Bibi Zhang, Qiuning Lin, Qi Bian, Yuxin Yin, Fangting Zuo, Ni Su, Yun Tang, Yuzheng Zhao, Yi Yang, Xianjun Chen, Linyong Zhu

{"title":"NirFAP680: a highly bright and stable large Stokes shift near-infrared fluorogen-activating protein.","authors":"Zhengda Chen, Li Jiang, Xiaoyu Liu, Yajie Shi, Yang Liu, Ling Jiang, Jiaxin Li, Xinyi Huang, Siyu Zhou, Bingkun Bao, Bibi Zhang, Qiuning Lin, Qi Bian, Yuxin Yin, Fangting Zuo, Ni Su, Yun Tang, Yuzheng Zhao, Yi Yang, Xianjun Chen, Linyong Zhu","doi":"10.1038/s41592-026-03061-6","DOIUrl":"https://doi.org/10.1038/s41592-026-03061-6","url":null,"abstract":"Near-infrared (NIR) genetically encoded fluorescent tags are superior for new imaging capabilities ranging from multiplexed imaging to deep-tissue imaging. Here, we describe the development of NirFAP680; NirFAP680 is an NIR fluorogen-activating protein (FAP) that consists of a newly designed NIR fluorogen termed HBMT and an engineered protein tag termed NirFAP. NirFAP680 has an order of magnitude greater cellular brightness and superior photostability compared to currently available NIR FAPs and fluorescent proteins in both single- and two-photon excitation and allows robust imaging of proteins in live cells and in vivo. Owing to its unique spectroscopic property of a >100 nm Stokes shift, NirFAP680 can also serve as a superb receptor for fluorescence or bioluminescence resonance energy transfer, allowing real-time monitoring of protein-protein interactions in live cells and sensitive bioluminescence imaging in vivo, respectively. Therefore, NirFAP680 will likely be useful for advanced biological imaging in live cells and in vivo.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":32.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777023","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

Multifactor authentication in extracellular vesicle analysis: methods and approaches to address the heterogeneity problem. 细胞外囊泡分析中的多因素鉴定：解决异质性问题的方法和途径。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-21 DOI: 10.1038/s41592-026-03068-z

Quan Zhou, Richard J Lobb, Alain Wuethrich, Matt Trau

{"title":"Multifactor authentication in extracellular vesicle analysis: methods and approaches to address the heterogeneity problem.","authors":"Quan Zhou, Richard J Lobb, Alain Wuethrich, Matt Trau","doi":"10.1038/s41592-026-03068-z","DOIUrl":"https://doi.org/10.1038/s41592-026-03068-z","url":null,"abstract":"Extracellular vesicles (EVs) are essential for intercellular communication and various physiological processes; however, they are difficult to reliably identify and characterize owing to their inherent heterogeneity. To address this challenge, we adapt the concept of multifactor authentication (MFA) from computer science, and apply it to EV analysis. Similar to requiring multiple credentials to confirm digital identity, MFA in EV research integrates structural and molecular features to validate vesicle identity within heterogeneous mixtures and resolve subpopulations down to the single-EV level. By cross-validating across distinct factors and standardizing a multistep pipeline, MFA has the potential to enhance specificity, reliability, reproducibility and biological interpretability in EV analysis. Although no single approach fulfills all MFA criteria, several existing approaches embody MFA-like features. In this Perspective, we introduce MFA, discuss MFA-like approaches for EV subpopulation and single-EV analyses, highlight implications for EV biology and translational applications, and outline future directions for implementing an idealized MFA framework.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":32.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776965","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

Scientists who decide to pick up and move. 决定收拾行装的科学家。

IF 32.1 1区生物学

Nature Methods Pub Date : 2026-04-17 DOI: 10.1038/s41592-026-03087-w

Vivien Marx

引用次数: 0