Pei Su, Michael A. R. Hollas, Indira Pla, Stanislav Rubakhin, Fatma Ayaloglu Butun, Joseph B. Greer, Bryan P. Early, Ryan T. Fellers, Michael A. Caldwell, Jonathan V. Sweedler, Jared O. Kafader, Neil L. Kelleher
{"title":"Proteoform profiling of endogenous single cells from rat hippocampus at scale","authors":"Pei Su, Michael A. R. Hollas, Indira Pla, Stanislav Rubakhin, Fatma Ayaloglu Butun, Joseph B. Greer, Bryan P. Early, Ryan T. Fellers, Michael A. Caldwell, Jonathan V. Sweedler, Jared O. Kafader, Neil L. Kelleher","doi":"10.1038/s41587-025-02669-x","DOIUrl":"https://doi.org/10.1038/s41587-025-02669-x","url":null,"abstract":"<p>We perform intact proteoform profiling of 10,809 endogenous single cells from the rat hippocampus using single-cell proteoform imaging mass spectrometry (scPiMS). scPiMS directly extracts whole proteins and demonstrates high throughput for MS-based single-cell proteomics compared with existing approaches. We develop an informatics workflow dedicated to this datatype and use it to assign neurons, astrocytes or microglia cell types according to their proteoform signatures.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"12 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979370","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}
{"title":"Targeting a cell surface RNA-binding protein driving acute myeloid leukemia","authors":"","doi":"10.1038/s41587-025-02695-9","DOIUrl":"https://doi.org/10.1038/s41587-025-02695-9","url":null,"abstract":"How modifications to RNA molecules and the proteins they interact with on the cell surface contribute to cancer is largely unknown. Preclinical evidence indicates that cell surface nucleophosmin (NPM1, an RNA-binding protein) is a novel druggable biomarker in acute myeloid leukemia, with potential implications for improving detection and immunotherapy strategies for several cancer types.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"240 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933283","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}
Lei Chang, Yang Xie, Brett Taylor, Zhaoning Wang, Jiachen Sun, Ethan J. Armand, Shreya Mishra, Jie Xu, Melodi Tastemel, Audrey Lie, Zane A. Gibbs, Hannah S. Indralingam, Tuyet M. Tan, Rafael Bejar, Clark C. Chen, Frank B. Furnari, Ming Hu, Bing Ren
{"title":"Author Correction: Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues","authors":"Lei Chang, Yang Xie, Brett Taylor, Zhaoning Wang, Jiachen Sun, Ethan J. Armand, Shreya Mishra, Jie Xu, Melodi Tastemel, Audrey Lie, Zane A. Gibbs, Hannah S. Indralingam, Tuyet M. Tan, Rafael Bejar, Clark C. Chen, Frank B. Furnari, Ming Hu, Bing Ren","doi":"10.1038/s41587-025-02697-7","DOIUrl":"https://doi.org/10.1038/s41587-025-02697-7","url":null,"abstract":"<p>Correction to: <i>Nature Biotechnology</i> https://doi.org/10.1038/s41587-024-02447-1, published online 18 October 2024.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"44 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933277","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}
{"title":"A protein association atlas for human tissues","authors":"","doi":"10.1038/s41587-025-02692-y","DOIUrl":"https://doi.org/10.1038/s41587-025-02692-y","url":null,"abstract":"Proteomics samples of human cancer biopsies were combined to derive an atlas of protein–protein associations for human tissues. Differences between tissues are not strongly driven by gene expression but could, in part, be due to tissue-specific subcellular components and processes.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"3 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933278","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}
Soumya Kannan, Han Altae-Tran, Shiyou Zhu, Peiyu Xu, Daniel Strebinger, Rachel Oshiro, Guilhem Faure, Lukas Moeller, Julie Pham, Kepler S. Mears, Heyuan M. Ni, Rhiannon K. Macrae, Feng Zhang
{"title":"Evolution-guided protein design of IscB for persistent epigenome editing in vivo","authors":"Soumya Kannan, Han Altae-Tran, Shiyou Zhu, Peiyu Xu, Daniel Strebinger, Rachel Oshiro, Guilhem Faure, Lukas Moeller, Julie Pham, Kepler S. Mears, Heyuan M. Ni, Rhiannon K. Macrae, Feng Zhang","doi":"10.1038/s41587-025-02655-3","DOIUrl":"https://doi.org/10.1038/s41587-025-02655-3","url":null,"abstract":"<p>Naturally existing enzymes have been adapted for a variety of molecular technologies, with enhancements or modifications to the enzymes introduced to improve the desired function; however, it is difficult to engineer variants with enhanced activity while maintaining specificity. Here we engineer the compact Obligate Mobile Element Guided Activity (OMEGA) RNA-guided endonuclease IscB and its guiding RNA (ωRNA) by combining ortholog screening, structure-guided protein domain design and RNA engineering, and deep learning-based structure prediction to generate an improved variant, NovaIscB. We show that the compact NovaIscB achieves up to 40% indel activity (~100-fold improvement over wild-type OgeuIscB) on the human genome with improved specificity relative to existing IscBs. We further show that NovaIscB can be fused with a methyltransferase to create a programmable transcriptional repressor, OMEGAoff, that is compact enough to be packaged in a single adeno-associated virus vector for persistent in vivo gene repression. This study highlights the power of combining natural diversity with protein engineering to design enhanced enzymes for molecular biology applications.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"116 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915841","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}
Roger A. Barker, Nicholas P. Lao-Kaim, Natalie Valle Guzman, Dilan Athauda, Hjalmar Bjartmarz, Anders Björklund, Alistair Church, Emma Cutting, Danielle Daft, Viswas Dayal, Stephen Dunnett, Amy Evans, Shane Grealish, Naomi Hannaway, Xiaoling He, Sam Hewitt, Zinovia Kefalopoulou, Philipp Mahlknecht, Antonio Martín-Bastida, Krista Farrell, Sarah Moore, Harry Bulstrode, Tagore Nakornchai, Jenny Nelander-Wahlestedt, Linnea Roupé, Gesine Paul, Kathryn Peall, Anne Rosser, Adriana Roca-Fernández, Sophie Rowlands, Anne-Marie McGorrian, Caroline Scherf, Ngoc Nga Vinh, Victoria Roberton, Claire Kelly, Mariah Lelos, Eduardo Torres, Kate Shires, Rachel Hills, Debbie Williams, Andreas-Antonios Roussakis, Krista Sibley, Pamela Tyers, Ruwani Wijeyekoon, Caroline Williams-Gray, Thomas Foltynie, Paola Piccini, Robert Morris, Stanley E. Lazic, Olle Lindvall, Malin Parmar, Hakan Widner
{"title":"The TransEuro open-label trial of human fetal ventral mesencephalic transplantation in patients with moderate Parkinson’s disease","authors":"Roger A. Barker, Nicholas P. Lao-Kaim, Natalie Valle Guzman, Dilan Athauda, Hjalmar Bjartmarz, Anders Björklund, Alistair Church, Emma Cutting, Danielle Daft, Viswas Dayal, Stephen Dunnett, Amy Evans, Shane Grealish, Naomi Hannaway, Xiaoling He, Sam Hewitt, Zinovia Kefalopoulou, Philipp Mahlknecht, Antonio Martín-Bastida, Krista Farrell, Sarah Moore, Harry Bulstrode, Tagore Nakornchai, Jenny Nelander-Wahlestedt, Linnea Roupé, Gesine Paul, Kathryn Peall, Anne Rosser, Adriana Roca-Fernández, Sophie Rowlands, Anne-Marie McGorrian, Caroline Scherf, Ngoc Nga Vinh, Victoria Roberton, Claire Kelly, Mariah Lelos, Eduardo Torres, Kate Shires, Rachel Hills, Debbie Williams, Andreas-Antonios Roussakis, Krista Sibley, Pamela Tyers, Ruwani Wijeyekoon, Caroline Williams-Gray, Thomas Foltynie, Paola Piccini, Robert Morris, Stanley E. Lazic, Olle Lindvall, Malin Parmar, Hakan Widner","doi":"10.1038/s41587-025-02567-2","DOIUrl":"https://doi.org/10.1038/s41587-025-02567-2","url":null,"abstract":"<p>Transplantation of human fetal ventral mesencephalic tissue in individuals with Parkinson’s disease has yielded clinical benefits but also side effects, such as graft-induced dyskinesias. The open-label TransEuro trial (NCT01898390) was designed to determine whether this approach could be further developed into a clinically useful treatment. Owing to poor availability of human fetal ventral mesencephalic tissue, only 11 individuals were grafted at two centers using the same tissue preparation protocol but different implantation devices. No overall clinical effect was seen for the primary endpoint 3 years after grafting. No major graft-induced dyskinesias were seen, but we observed differences in outcome related to transplant device and/or site. Mean dopamine uptake improved at 18 months in seven individuals according to [<sup>18</sup>F]fluorodopa positron emission tomography imaging but was restored to near-normal levels in only one individual. Our findings highlight the need for a stem cell source of dopamine neurons for potential Parkinson’s disease cell therapy and provide critical insights into how such clinical studies should be approached.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"138 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898170","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}
Diederik S. Laman Trip, Marc van Oostrum, Danish Memon, Fabian Frommelt, Delora Baptista, Kalpana Panneerselvam, Glyn Bradley, Luana Licata, Henning Hermjakob, Sandra Orchard, Gosia Trynka, Ellen M. McDonagh, Andrea Fossati, Ruedi Aebersold, Matthias Gstaiger, Bernd Wollscheid, Pedro Beltrao
{"title":"A tissue-specific atlas of protein–protein associations enables prioritization of candidate disease genes","authors":"Diederik S. Laman Trip, Marc van Oostrum, Danish Memon, Fabian Frommelt, Delora Baptista, Kalpana Panneerselvam, Glyn Bradley, Luana Licata, Henning Hermjakob, Sandra Orchard, Gosia Trynka, Ellen M. McDonagh, Andrea Fossati, Ruedi Aebersold, Matthias Gstaiger, Bernd Wollscheid, Pedro Beltrao","doi":"10.1038/s41587-025-02659-z","DOIUrl":"https://doi.org/10.1038/s41587-025-02659-z","url":null,"abstract":"<p>Despite progress in mapping protein–protein interactions, their tissue specificity is understudied. Here, given that protein coabundance is predictive of functional association, we compiled and analyzed protein abundance data of 7,811 proteomic samples from 11 human tissues to produce an atlas of tissue-specific protein associations. We find that this method recapitulates known protein complexes and the larger structural organization of the cell. Interactions of stable protein complexes are well preserved across tissues, while cell-type-specific cellular structures, such as synaptic components, are found to represent a substantial driver of differences between tissues. Over 25% of associations are tissue specific, of which <7% are because of differences in gene expression. We validate protein associations for the brain through cofractionation experiments in synaptosomes, curation of brain-derived pulldown data and AlphaFold2 modeling. We also construct a network of brain interactions for schizophrenia-related genes, indicating that our approach can functionally prioritize candidate disease genes in loci linked to brain disorders.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"111 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898176","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}
{"title":"A mini-colon models colon cancer and its microenvironment.","authors":"Colin Hutton, Vivian S W Li","doi":"10.1038/s41587-024-02343-8","DOIUrl":"10.1038/s41587-024-02343-8","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":"686-688"},"PeriodicalIF":33.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760012","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}
{"title":"CRISPR screens of tumor-infiltrating NK cells identify genetic checkpoints for CAR-NK therapy.","authors":"","doi":"10.1038/s41587-024-02319-8","DOIUrl":"10.1038/s41587-024-02319-8","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":"696-697"},"PeriodicalIF":33.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450981","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}
Nicolas Mathis, Ahmed Allam, András Tálas, Lucas Kissling, Elena Benvenuto, Lukas Schmidheini, Ruben Schep, Tanav Damodharan, Zsolt Balázs, Sharan Janjuha, Eleonora I Ioannidi, Desirée Böck, Bas van Steensel, Michael Krauthammer, Gerald Schwank
{"title":"Publisher Correction: Machine learning prediction of prime editing efficiency across diverse chromatin contexts.","authors":"Nicolas Mathis, Ahmed Allam, András Tálas, Lucas Kissling, Elena Benvenuto, Lukas Schmidheini, Ruben Schep, Tanav Damodharan, Zsolt Balázs, Sharan Janjuha, Eleonora I Ioannidi, Desirée Böck, Bas van Steensel, Michael Krauthammer, Gerald Schwank","doi":"10.1038/s41587-024-02383-0","DOIUrl":"10.1038/s41587-024-02383-0","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":" ","pages":"822"},"PeriodicalIF":33.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971523","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}
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