Nature MethodsPub Date : 2025-01-27DOI: 10.1038/s41592-024-02571-5
Maren Salla, Klara Penkert, Leif S. Ludwig
{"title":"The next generation of in situ multi-omics","authors":"Maren Salla, Klara Penkert, Leif S. Ludwig","doi":"10.1038/s41592-024-02571-5","DOIUrl":"10.1038/s41592-024-02571-5","url":null,"abstract":"Spatial-Mux-seq adds to a growing portfolio of innovative spatial omics technologies and enables simultaneous profiling of up to five omic modalities in situ.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 3","pages":"461-462"},"PeriodicalIF":36.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052607","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}
Nature MethodsPub Date : 2025-01-24DOI: 10.1038/s41592-025-02601-w
Cheng Zhao, Alvaro Plaza Reyes, John Paul Schell, Jere Weltner, Nicolás M. Ortega, Yi Zheng, Åsa K. Björklund, Laura Baqué-Vidal, Joonas Sokka, Ras Trokovic, Brian Cox, Janet Rossant, Jianping Fu, Sophie Petropoulos, Fredrik Lanner
{"title":"Author Correction: A comprehensive human embryo reference tool using single-cell RNA-sequencing data","authors":"Cheng Zhao, Alvaro Plaza Reyes, John Paul Schell, Jere Weltner, Nicolás M. Ortega, Yi Zheng, Åsa K. Björklund, Laura Baqué-Vidal, Joonas Sokka, Ras Trokovic, Brian Cox, Janet Rossant, Jianping Fu, Sophie Petropoulos, Fredrik Lanner","doi":"10.1038/s41592-025-02601-w","DOIUrl":"10.1038/s41592-025-02601-w","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 3","pages":"636-636"},"PeriodicalIF":36.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41592-025-02601-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039460","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}
Nature MethodsPub Date : 2025-01-24DOI: 10.1038/s41592-025-02600-x
Kyle Coleman, Amelia Schroeder, Melanie Loth, Daiwei Zhang, Jeong Hwan Park, Ji-Youn Sung, Niklas Blank, Alexis J. Cowan, Xuyu Qian, Jianfeng Chen, Jiahui Jiang, Hanying Yan, Laith Z. Samarah, Jean R. Clemenceau, Inyeop Jang, Minji Kim, Isabel Barnfather, Joshua D. Rabinowitz, Yanxiang Deng, Edward B. Lee, Alexander Lazar, Jianjun Gao, Emma E. Furth, Tae Hyun Hwang, Linghua Wang, Christoph A. Thaiss, Jian Hu, Mingyao Li
{"title":"Author Correction: Resolving tissue complexity by multimodal spatial omics modeling with MISO","authors":"Kyle Coleman, Amelia Schroeder, Melanie Loth, Daiwei Zhang, Jeong Hwan Park, Ji-Youn Sung, Niklas Blank, Alexis J. Cowan, Xuyu Qian, Jianfeng Chen, Jiahui Jiang, Hanying Yan, Laith Z. Samarah, Jean R. Clemenceau, Inyeop Jang, Minji Kim, Isabel Barnfather, Joshua D. Rabinowitz, Yanxiang Deng, Edward B. Lee, Alexander Lazar, Jianjun Gao, Emma E. Furth, Tae Hyun Hwang, Linghua Wang, Christoph A. Thaiss, Jian Hu, Mingyao Li","doi":"10.1038/s41592-025-02600-x","DOIUrl":"10.1038/s41592-025-02600-x","url":null,"abstract":"","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 3","pages":"635-635"},"PeriodicalIF":36.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41592-025-02600-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039462","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}
Nature MethodsPub Date : 2025-01-23DOI: 10.1038/s41592-024-02503-3
Uthsav Chitra, Brian J. Arnold, Hirak Sarkar, Kohei Sanno, Cong Ma, Sereno Lopez-Darwin, Benjamin J. Raphael
{"title":"Mapping the topography of spatial gene expression with interpretable deep learning","authors":"Uthsav Chitra, Brian J. Arnold, Hirak Sarkar, Kohei Sanno, Cong Ma, Sereno Lopez-Darwin, Benjamin J. Raphael","doi":"10.1038/s41592-024-02503-3","DOIUrl":"10.1038/s41592-024-02503-3","url":null,"abstract":"Spatially resolved transcriptomics technologies provide high-throughput measurements of gene expression in a tissue slice, but the sparsity of these data complicates analysis of spatial gene expression patterns. We address this issue by deriving a topographic map of a tissue slice—analogous to a map of elevation in a landscape—using a quantity called the isodepth. Contours of constant isodepths enclose domains with distinct cell type composition, while gradients of the isodepth indicate spatial directions of maximum change in expression. We develop GASTON (gradient analysis of spatial transcriptomics organization with neural networks), an unsupervised and interpretable deep learning algorithm that simultaneously learns the isodepth, spatial gradients and piecewise linear expression functions that model both continuous gradients and discontinuous variation in gene expression. We show that GASTON accurately identifies spatial domains and marker genes across several tissues, gradients of neuronal differentiation and firing in the brain, and gradients of metabolism and immune activity in the tumor microenvironment. Gene expression topography analysis by GASTON portrays domain organization and spatial gradients of gene expression and cell type composition using spatially resolved transcriptomics data.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 2","pages":"298-309"},"PeriodicalIF":36.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029207","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}
Nature MethodsPub Date : 2025-01-23DOI: 10.1038/s41592-024-02573-3
{"title":"Precision control of cellular functions with a temperature-sensitive protein","authors":"","doi":"10.1038/s41592-024-02573-3","DOIUrl":"10.1038/s41592-024-02573-3","url":null,"abstract":"Temperature-sensitive proteins would enable the remote control of cellular functions deep within tissues, although few such proteins have been characterized. Melt is a protein that reversibly clusters and translocates to the membrane in response to small temperature changes, enabling flexible regulation of cellular processes in vitro and in vivo.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 3","pages":"465-466"},"PeriodicalIF":36.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029222","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}
Nature MethodsPub Date : 2025-01-23DOI: 10.1038/s41592-024-02572-4
William Benman, Zikang Huang, Pavan Iyengar, Delaney Wilde, Thomas R. Mumford, Lukasz J. Bugaj
{"title":"A temperature-inducible protein module for control of mammalian cell fate","authors":"William Benman, Zikang Huang, Pavan Iyengar, Delaney Wilde, Thomas R. Mumford, Lukasz J. Bugaj","doi":"10.1038/s41592-024-02572-4","DOIUrl":"10.1038/s41592-024-02572-4","url":null,"abstract":"Inducible protein switches are currently limited for use in tissues and organisms because common inducers cannot be controlled with precision in space and time in optically dense settings. Here, we introduce a protein that can be reversibly toggled with a small change in temperature, a stimulus that is both penetrant and dynamic. This protein, called Melt (Membrane localization using temperature) oligomerizes and translocates to the plasma membrane when temperature is lowered. We generated a library of Melt variants with switching temperatures ranging from 30 °C to 40 °C, including two that operate at and above 37 °C. Melt was a highly modular actuator of cell function, permitting thermal control over diverse processes including signaling, proteolysis, nuclear shuttling, cytoskeletal rearrangements and cell death. Finally, Melt permitted thermal control of cell death in a mouse model of human cancer. Melt represents a versatile thermogenetic module for straightforward, non-invasive and spatiotemporally defined control of mammalian cells with broad potential for biotechnology and biomedicine. The Melt (Membrane localization using temperature) protein translocates to the plasma membrane upon temperature shift. Melt variants with a range of switching temperatures enable straightforward thermogenetic control of diverse cellular processes.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 3","pages":"539-549"},"PeriodicalIF":36.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029206","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}
Nature MethodsPub Date : 2025-01-20DOI: 10.1038/s41592-024-02586-y
Yun Li, Zheng Huang, Lubin Xu, Yanling Fan, Jun Ping, Guochao Li, Yanjie Chen, Chengwei Yu, Qifei Wang, Turun Song, Tao Lin, Mengmeng Liu, Yangqing Xu, Na Ai, Xini Meng, Qin Qiao, Hongbin Ji, Zhen Qin, Shuo Jin, Nan Jiang, Minxian Wang, Shaokun Shu, Feng Zhang, Weiqi Zhang, Guang-Hui Liu, Limeng Chen, Lan Jiang
{"title":"UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing.","authors":"Yun Li, Zheng Huang, Lubin Xu, Yanling Fan, Jun Ping, Guochao Li, Yanjie Chen, Chengwei Yu, Qifei Wang, Turun Song, Tao Lin, Mengmeng Liu, Yangqing Xu, Na Ai, Xini Meng, Qin Qiao, Hongbin Ji, Zhen Qin, Shuo Jin, Nan Jiang, Minxian Wang, Shaokun Shu, Feng Zhang, Weiqi Zhang, Guang-Hui Liu, Limeng Chen, Lan Jiang","doi":"10.1038/s41592-024-02586-y","DOIUrl":"10.1038/s41592-024-02586-y","url":null,"abstract":"<p><p>The use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods. UDA-seq was benchmarked across various tissue and cell types, enabling several common multimodal analyses, including single-cell co-assay of RNA and VDJ, RNA and chromatin, and RNA and CRISPR perturbation. Notably, UDA-seq facilitated the efficient generation of over 100,000 high-quality single-cell datasets from three dozen frozen clinical biopsy specimens within a single-channel droplet microfluidics experiment. Downstream analysis demonstrated the robustness of this approach in identifying rare cell subpopulations associated with clinical phenotypes and exploring the vulnerability of cancer cells.</p>","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":" ","pages":""},"PeriodicalIF":36.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008736","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}
Nature MethodsPub Date : 2025-01-20DOI: 10.1038/s41592-024-02518-w
{"title":"Capture of membrane proteins in their native membrane milieu","authors":"","doi":"10.1038/s41592-024-02518-w","DOIUrl":"10.1038/s41592-024-02518-w","url":null,"abstract":"This work presents optimized experimental protocols for the extraction of >2,000 unique membrane proteins directly from their native membranes into native nanodiscs. Combined with orthogonal structural, biochemical or biophysical approaches, these native nanodiscs enable membrane proteins to be studied directly in their native membrane context.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"22 2","pages":"237-238"},"PeriodicalIF":36.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008029","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}