Pub Date : 2025-11-27DOI: 10.1038/s41580-025-00934-0
Na Sun
Artificial intelligence (AI) offers new opportunities to model inter-organ communication and systemic biology. Integrating experimental advances with computational modelling presents key challenges, and here I propose future directions for building predictive, interpretable and generative frameworks that bridge molecular data to organism-level insights. In this Comment, Na Sun explores how artificial intelligence-driven methodologies are poised to transform systems biology, particularly in the realm of tissue modelling, and outlines the key challenges that must be overcome to enable the development of truly predictive biological systems.
{"title":"Challenges and potential applications of AI in systems biology","authors":"Na Sun","doi":"10.1038/s41580-025-00934-0","DOIUrl":"10.1038/s41580-025-00934-0","url":null,"abstract":"Artificial intelligence (AI) offers new opportunities to model inter-organ communication and systemic biology. Integrating experimental advances with computational modelling presents key challenges, and here I propose future directions for building predictive, interpretable and generative frameworks that bridge molecular data to organism-level insights. In this Comment, Na Sun explores how artificial intelligence-driven methodologies are poised to transform systems biology, particularly in the realm of tissue modelling, and outlines the key challenges that must be overcome to enable the development of truly predictive biological systems.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 2","pages":"89-90"},"PeriodicalIF":90.2,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609204","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}
Pub Date : 2025-11-27DOI: 10.1038/s41580-025-00935-z
Shiri Gur-Cohen
{"title":"Like water on rock, the microenvironment bends stem cell fate","authors":"Shiri Gur-Cohen","doi":"10.1038/s41580-025-00935-z","DOIUrl":"https://doi.org/10.1038/s41580-025-00935-z","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"5 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609461","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}
Pub Date : 2025-11-26DOI: 10.1038/s41580-025-00909-1
M. Burigotto, J. G. Carlton
{"title":"ESCRT-III function in membrane fission and repair","authors":"M. Burigotto, J. G. Carlton","doi":"10.1038/s41580-025-00909-1","DOIUrl":"https://doi.org/10.1038/s41580-025-00909-1","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"3 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599437","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}
Pub Date : 2025-11-20DOI: 10.1038/s41580-025-00897-2
Christopher Chin Sang,Sayantani Upadhyay,Michael L Nosella,Julie D Forman-Kay,Hyun O Lee
Biomolecular condensates are non-membrane-encapsulated compartments that control various biological processes, largely by enriching and excluding certain molecules. Emerging evidence demonstrates that condensate compositions dynamically change in response to stimuli and over time. Thus, condensates that share a designation and general function can substantially vary in their composition. In this Review, we discuss the current understanding of condensate composition changes and heterogeneity, how they are regulated and how the changes affect biochemical reactions. We focus on four condensates: DNA double-strand break (DSB) repair foci, promyelocytic leukaemia (PML) nuclear bodies, processing bodies (P-bodies) and RNA transport granules, with examples from stress granules and germ granules. Changes in condensate composition seem to support complex reactions, such as those occurring in DNA repair and RNA processing. Mechanisms regulating composition changes include biophysical features of components, modifications, nodes and enzymatic reactions. We also speculate about the impact of protein mislocalization and mutations on condensate composition and function, including in cancer and neurodegenerative diseases. We conclude by discussing outstanding questions and the implications of studying condensate composition changes for research and therapeutics.
{"title":"The dynamic and heterogeneous composition of biomolecular condensates and its functional relevance.","authors":"Christopher Chin Sang,Sayantani Upadhyay,Michael L Nosella,Julie D Forman-Kay,Hyun O Lee","doi":"10.1038/s41580-025-00897-2","DOIUrl":"https://doi.org/10.1038/s41580-025-00897-2","url":null,"abstract":"Biomolecular condensates are non-membrane-encapsulated compartments that control various biological processes, largely by enriching and excluding certain molecules. Emerging evidence demonstrates that condensate compositions dynamically change in response to stimuli and over time. Thus, condensates that share a designation and general function can substantially vary in their composition. In this Review, we discuss the current understanding of condensate composition changes and heterogeneity, how they are regulated and how the changes affect biochemical reactions. We focus on four condensates: DNA double-strand break (DSB) repair foci, promyelocytic leukaemia (PML) nuclear bodies, processing bodies (P-bodies) and RNA transport granules, with examples from stress granules and germ granules. Changes in condensate composition seem to support complex reactions, such as those occurring in DNA repair and RNA processing. Mechanisms regulating composition changes include biophysical features of components, modifications, nodes and enzymatic reactions. We also speculate about the impact of protein mislocalization and mutations on condensate composition and function, including in cancer and neurodegenerative diseases. We conclude by discussing outstanding questions and the implications of studying condensate composition changes for research and therapeutics.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"30 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559025","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}
Pub Date : 2025-11-18DOI: 10.1038/s41580-025-00915-3
Marjolein van Sluis, Camila Gonzalo-Hansen, Qingrong Li, Hannes Lans, Dong Wang, Jurgen A. Marteijn
{"title":"Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease","authors":"Marjolein van Sluis, Camila Gonzalo-Hansen, Qingrong Li, Hannes Lans, Dong Wang, Jurgen A. Marteijn","doi":"10.1038/s41580-025-00915-3","DOIUrl":"https://doi.org/10.1038/s41580-025-00915-3","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"155 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536095","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}
Pub Date : 2025-11-12DOI: 10.1038/s41580-025-00928-y
Timo N. Kohler
{"title":"From pluripotency to species conservation","authors":"Timo N. Kohler","doi":"10.1038/s41580-025-00928-y","DOIUrl":"https://doi.org/10.1038/s41580-025-00928-y","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"53 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492631","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}
Pub Date : 2025-11-11DOI: 10.1038/s41580-025-00930-4
Mengxi Zhang
In this Tools of the Trade article, Zhang (Xiao Lab) highlights the development of a rotor-based fluorescent amino acid that acts as a sensor for crowded protein microenvironments, enabling researchers to monitor protein behaviour in vivo.
{"title":"Illuminating protein microenvironments with rotor-based fluorescent amino acids","authors":"Mengxi Zhang","doi":"10.1038/s41580-025-00930-4","DOIUrl":"10.1038/s41580-025-00930-4","url":null,"abstract":"In this Tools of the Trade article, Zhang (Xiao Lab) highlights the development of a rotor-based fluorescent amino acid that acts as a sensor for crowded protein microenvironments, enabling researchers to monitor protein behaviour in vivo.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"27 2","pages":"92-92"},"PeriodicalIF":90.2,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484713","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}
Pub Date : 2025-11-11DOI: 10.1038/s41580-025-00917-1
Sushant Bangru,Rocky Diegmiller,Stefano Di Talia,Kenneth D Poss
Tissue regeneration has historically been the subject of intense scientific scrutiny, from basic biology to applications in regenerative medicine. Use of model organisms and cutting-edge technologies have uncovered various mechanisms of regeneration, but understanding how signals are regulated spatiotemporally to renew lost structures at scale remains a challenge. Recent insights into chromatin structure and enhancer regulation, immune-tissue crosstalk, bioelectric and metabolic cues and quantitative modelling are broadening and reshaping our understanding of how tissues repair and renew. The evolution of cutting-edge tools for in vivo profiling and tracking of single cells is providing unprecedented dynamic views of regeneration across scales. Here, we synthesize the current knowledge of signal control in regeneration, with emphasis on conceptual advances, technical innovations and future directions for a more quantitative understanding of regenerative biology.
{"title":"Signal control during tissue regeneration in adult animals.","authors":"Sushant Bangru,Rocky Diegmiller,Stefano Di Talia,Kenneth D Poss","doi":"10.1038/s41580-025-00917-1","DOIUrl":"https://doi.org/10.1038/s41580-025-00917-1","url":null,"abstract":"Tissue regeneration has historically been the subject of intense scientific scrutiny, from basic biology to applications in regenerative medicine. Use of model organisms and cutting-edge technologies have uncovered various mechanisms of regeneration, but understanding how signals are regulated spatiotemporally to renew lost structures at scale remains a challenge. Recent insights into chromatin structure and enhancer regulation, immune-tissue crosstalk, bioelectric and metabolic cues and quantitative modelling are broadening and reshaping our understanding of how tissues repair and renew. The evolution of cutting-edge tools for in vivo profiling and tracking of single cells is providing unprecedented dynamic views of regeneration across scales. Here, we synthesize the current knowledge of signal control in regeneration, with emphasis on conceptual advances, technical innovations and future directions for a more quantitative understanding of regenerative biology.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"54 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491606","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}
Pub Date : 2025-11-10DOI: 10.1038/s41580-025-00907-3
Emma T. Watson, William R. Wegeng, Stamatina Aravani, Andreas M. Ernst, Julia von Blume
The Golgi apparatus has a central role in the formation and trafficking of glycoproteins and lipids. It is organized into a series of flattened, membrane-bound compartments called cisternae, each housing a unique set of resident proteins that sequentially modify newly synthesized proteins and lipids as they move through the Golgi stack. In the final compartments, known as the trans-Golgi network (TGN), the processed cargoes are sorted and packaged into transport carriers. Despite substantial progress, key questions remain about how proteins and lipids are selectively sorted within the Golgi for delivery to specific destinations. In this Review we highlight recent insights on the biogenesis of membrane carriers at the TGN that enable transport of macromolecules along the secretory pathway and discuss how dysfunction of the molecular machinery gives rise to Golgi-related diseases. Protein and lipid cargoes are modified and sorted in the Golgi apparatus and packaged for delivery to diverse cellular destinations at the trans-Golgi network (TGN). This Review discusses recent insights into Golgi transport mechanisms and carrier biogenesis at the TGN.
{"title":"Mechanistic insights into cargo sorting and export from the Golgi apparatus","authors":"Emma T. Watson, William R. Wegeng, Stamatina Aravani, Andreas M. Ernst, Julia von Blume","doi":"10.1038/s41580-025-00907-3","DOIUrl":"10.1038/s41580-025-00907-3","url":null,"abstract":"The Golgi apparatus has a central role in the formation and trafficking of glycoproteins and lipids. It is organized into a series of flattened, membrane-bound compartments called cisternae, each housing a unique set of resident proteins that sequentially modify newly synthesized proteins and lipids as they move through the Golgi stack. In the final compartments, known as the trans-Golgi network (TGN), the processed cargoes are sorted and packaged into transport carriers. Despite substantial progress, key questions remain about how proteins and lipids are selectively sorted within the Golgi for delivery to specific destinations. In this Review we highlight recent insights on the biogenesis of membrane carriers at the TGN that enable transport of macromolecules along the secretory pathway and discuss how dysfunction of the molecular machinery gives rise to Golgi-related diseases. Protein and lipid cargoes are modified and sorted in the Golgi apparatus and packaged for delivery to diverse cellular destinations at the trans-Golgi network (TGN). This Review discusses recent insights into Golgi transport mechanisms and carrier biogenesis at the TGN.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 12","pages":"940-956"},"PeriodicalIF":90.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145478132","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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