Pub Date : 2025-07-16DOI: 10.1038/s41576-025-00878-3
Jian Shu
In this Journal Club, Jian Shu recalls a 2006 publication by Takahashi and Yamanaka as well as a 2021 paper introducing AlphaFold to discuss the fascinating potential of cellular reprogramming in the age of artificial intelligence.
{"title":"When cellular reprogramming meets AI: towards de novo cell design","authors":"Jian Shu","doi":"10.1038/s41576-025-00878-3","DOIUrl":"10.1038/s41576-025-00878-3","url":null,"abstract":"In this Journal Club, Jian Shu recalls a 2006 publication by Takahashi and Yamanaka as well as a 2021 paper introducing AlphaFold to discuss the fascinating potential of cellular reprogramming in the age of artificial intelligence.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 9","pages":"585-585"},"PeriodicalIF":52.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640359","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 : 2025-07-15DOI: 10.1038/s41576-025-00877-4
Liyang Song (, )
Liyang Song presents gsMap, which integrates spatial transcriptomics (ST) data with GWAS summary statistics to assess whether genetic variants in or near genes specifically expressed in an ST data spot are enriched for genetic associations with a trait of interest.
{"title":"Mapping trait-associated cells with spatial transcriptomics","authors":"Liyang Song \u0000 (, )","doi":"10.1038/s41576-025-00877-4","DOIUrl":"10.1038/s41576-025-00877-4","url":null,"abstract":"Liyang Song presents gsMap, which integrates spatial transcriptomics (ST) data with GWAS summary statistics to assess whether genetic variants in or near genes specifically expressed in an ST data spot are enriched for genetic associations with a trait of interest.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 11","pages":"739-739"},"PeriodicalIF":52.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640200","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 : 2025-07-09DOI: 10.1038/s41576-025-00864-9
Maxwell C. Coyle, Nicole King
The development of a single-celled zygote into a complex, multicellular animal is directed by transcription factors and regulatory RNAs that coordinate spatio-temporal gene expression patterns. Given the morphological complexity of animals, some prior work has hypothesized that the origin of animals required the evolution of unique and markedly complex transcriptional regulatory mechanisms. Such postulated animal innovations include the evolution of greater numbers of transcription factors, new transcription factor families, distal enhancers and the emergence of long non-coding RNAs. Here, we revisit these explanations in light of new genomic and functional data from diverse early-branching animals and close relatives of animals, which provide essential phylogenetic context for reconstructing the origin of animals. These experimental models also offer examples of how some animal developmental pathways were built from core mechanisms inherited from their protistan ancestors. These new data provide fresh perspectives on whether animal origins entailed fundamental innovations in transcriptional regulation or whether, alternatively, a gradual accumulation of smaller changes sufficed to generate the complex developmental and cell differentiation mechanisms of early animals. In this Review, Coyle and King explore how genomic and functional data from diverse species are providing new insights into the types of mechanistic changes that accompanied the evolutionary origin of animals.
{"title":"The evolutionary foundations of transcriptional regulation in animals","authors":"Maxwell C. Coyle, Nicole King","doi":"10.1038/s41576-025-00864-9","DOIUrl":"10.1038/s41576-025-00864-9","url":null,"abstract":"The development of a single-celled zygote into a complex, multicellular animal is directed by transcription factors and regulatory RNAs that coordinate spatio-temporal gene expression patterns. Given the morphological complexity of animals, some prior work has hypothesized that the origin of animals required the evolution of unique and markedly complex transcriptional regulatory mechanisms. Such postulated animal innovations include the evolution of greater numbers of transcription factors, new transcription factor families, distal enhancers and the emergence of long non-coding RNAs. Here, we revisit these explanations in light of new genomic and functional data from diverse early-branching animals and close relatives of animals, which provide essential phylogenetic context for reconstructing the origin of animals. These experimental models also offer examples of how some animal developmental pathways were built from core mechanisms inherited from their protistan ancestors. These new data provide fresh perspectives on whether animal origins entailed fundamental innovations in transcriptional regulation or whether, alternatively, a gradual accumulation of smaller changes sufficed to generate the complex developmental and cell differentiation mechanisms of early animals. In this Review, Coyle and King explore how genomic and functional data from diverse species are providing new insights into the types of mechanistic changes that accompanied the evolutionary origin of animals.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 12","pages":"812-827"},"PeriodicalIF":52.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586308","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 : 2025-07-07DOI: 10.1038/s41576-025-00874-7
Mariangela Bonizzoni
Mariangela Bonizzoni recalls a 2004 paper by Crochu et al. that revealed non-retroviral integrations into eukaryotic genomics to be a widespread and complex phenomenon.
{"title":"Non-retroviral RNA viruses in eukaryotic genomes","authors":"Mariangela Bonizzoni","doi":"10.1038/s41576-025-00874-7","DOIUrl":"10.1038/s41576-025-00874-7","url":null,"abstract":"Mariangela Bonizzoni recalls a 2004 paper by Crochu et al. that revealed non-retroviral integrations into eukaryotic genomics to be a widespread and complex phenomenon.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 1","pages":"12-12"},"PeriodicalIF":52.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568720","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 : 2025-07-01DOI: 10.1038/s41576-025-00872-9
Nina Wedell
Nina Wedell discusses how a study by Dunning Hotopp et al., which found widespread lateral gene transfer (LGT) from the bacterium Wolbachia to a variety of arthropod and nematode hosts, catalysed the debate on the extent and functional relevance of LGT-derived genes.
{"title":"Harnessing lateral gene transfer and endosymbiosis for adaptation","authors":"Nina Wedell","doi":"10.1038/s41576-025-00872-9","DOIUrl":"10.1038/s41576-025-00872-9","url":null,"abstract":"Nina Wedell discusses how a study by Dunning Hotopp et al., which found widespread lateral gene transfer (LGT) from the bacterium Wolbachia to a variety of arthropod and nematode hosts, catalysed the debate on the extent and functional relevance of LGT-derived genes.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 12","pages":"811-811"},"PeriodicalIF":52.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521056","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 : 2025-06-30DOI: 10.1038/s41576-025-00862-x
Varun K. A. Sreenivasan, Verónica Yumiceba, Malte Spielmann
The spatial organization of the genome within the nucleus — also known as genome architecture or 3D genome — is important to the regulation of gene expression. Disruption of the 3D genome, for example, by structural variation, can contribute to disease, including developmental disorders and cancer. Structural variants can rearrange higher-order chromatin structures, such as topologically associating domains, and disrupt interactions between cis-regulatory elements, which can lead to altered gene expression, a phenomenon known as position effects. New experimental and computational approaches are revealing the effect of structural variants on the 3D genome and gene expression and can help interpret their pathogenic potential, which has important implications for patients. Here, we review mechanisms of disease caused by position effects owing to disruptions of genome architecture, and more specifically topologically associating domains, as well as their consequences and clinical impact. Disruption of the 3D genome caused by structural variation contributes to developmental disorders and cancer. The authors review the causes and molecular and clinical consequences of position effects arising from disruptions to the genome architecture.
{"title":"Structural variants in the 3D genome as drivers of disease","authors":"Varun K. A. Sreenivasan, Verónica Yumiceba, Malte Spielmann","doi":"10.1038/s41576-025-00862-x","DOIUrl":"10.1038/s41576-025-00862-x","url":null,"abstract":"The spatial organization of the genome within the nucleus — also known as genome architecture or 3D genome — is important to the regulation of gene expression. Disruption of the 3D genome, for example, by structural variation, can contribute to disease, including developmental disorders and cancer. Structural variants can rearrange higher-order chromatin structures, such as topologically associating domains, and disrupt interactions between cis-regulatory elements, which can lead to altered gene expression, a phenomenon known as position effects. New experimental and computational approaches are revealing the effect of structural variants on the 3D genome and gene expression and can help interpret their pathogenic potential, which has important implications for patients. Here, we review mechanisms of disease caused by position effects owing to disruptions of genome architecture, and more specifically topologically associating domains, as well as their consequences and clinical impact. Disruption of the 3D genome caused by structural variation contributes to developmental disorders and cancer. The authors review the causes and molecular and clinical consequences of position effects arising from disruptions to the genome architecture.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 11","pages":"742-760"},"PeriodicalIF":52.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515190","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 : 2025-06-25DOI: 10.1038/s41576-025-00868-5
Yodai Takei
In this Tools of the Trade article, Yodai Takei presents two-layer seqFISH+, an imaging method that uses a novel barcoding strategy to simultaneously profile chromatin organization, the transcriptome and subnuclear structures at single-cell resolution.
{"title":"Spatial multi-omics of nuclear architecture with two-layer seqFISH+","authors":"Yodai Takei","doi":"10.1038/s41576-025-00868-5","DOIUrl":"10.1038/s41576-025-00868-5","url":null,"abstract":"In this Tools of the Trade article, Yodai Takei presents two-layer seqFISH+, an imaging method that uses a novel barcoding strategy to simultaneously profile chromatin organization, the transcriptome and subnuclear structures at single-cell resolution.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 9","pages":"582-583"},"PeriodicalIF":52.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478960","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 : 2025-06-19DOI: 10.1038/s41576-025-00859-6
Karsten Rippe, Argyris Papantonis
Transcription by RNA polymerase II is a fundamental step in gene regulation that mainly occurs in discrete nuclear foci, or transcription compartments, characterized by a high local concentration of polymerases and nascent RNA. Early studies referred to these foci as transcription factories, proposing that they harbour most transcriptional activity and all relevant protein machinery to produce mature RNAs. However, this model of transcriptional organization has long remained controversial owing to its mechanistic uncertainties. Recently, new insights into how these foci may form are being provided by studies of phase-separated transcriptional condensates that encompass RNA polymerases, transcription factors and RNA. Advances in 3D genomics and chromatin imaging are also deepening our understanding of how transcription compartments might facilitate communication between cis-regulatory elements in 3D nuclear space. In this Review, we contrast historical work on transcription factories with recent findings on transcriptional condensates to better understand the architecture and functional relevance of transcription compartments. In this Review, Rippe and Papantonis describe advances in understanding the role of transcription compartments in gene regulation, specifically by collating and contrasting historical work on transcription factories with more recent work on transcriptional condensates.
{"title":"RNA polymerase II transcription compartments — from factories to condensates","authors":"Karsten Rippe, Argyris Papantonis","doi":"10.1038/s41576-025-00859-6","DOIUrl":"10.1038/s41576-025-00859-6","url":null,"abstract":"Transcription by RNA polymerase II is a fundamental step in gene regulation that mainly occurs in discrete nuclear foci, or transcription compartments, characterized by a high local concentration of polymerases and nascent RNA. Early studies referred to these foci as transcription factories, proposing that they harbour most transcriptional activity and all relevant protein machinery to produce mature RNAs. However, this model of transcriptional organization has long remained controversial owing to its mechanistic uncertainties. Recently, new insights into how these foci may form are being provided by studies of phase-separated transcriptional condensates that encompass RNA polymerases, transcription factors and RNA. Advances in 3D genomics and chromatin imaging are also deepening our understanding of how transcription compartments might facilitate communication between cis-regulatory elements in 3D nuclear space. In this Review, we contrast historical work on transcription factories with recent findings on transcriptional condensates to better understand the architecture and functional relevance of transcription compartments. In this Review, Rippe and Papantonis describe advances in understanding the role of transcription compartments in gene regulation, specifically by collating and contrasting historical work on transcription factories with more recent work on transcriptional condensates.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 11","pages":"775-788"},"PeriodicalIF":52.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319502","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 : 2025-06-16DOI: 10.1038/s41576-025-00866-7
Hakhamanesh Mostafavi
Hakhamanesh Mostafavi recalls a landmark paper by Boyle et al. on the omnigenic model, which proposed that complex traits are influenced by thousands of genes across the genome, including many that are only indirectly related to a trait through regulatory networks.
{"title":"Making sense of the polygenicity of complex traits","authors":"Hakhamanesh Mostafavi","doi":"10.1038/s41576-025-00866-7","DOIUrl":"10.1038/s41576-025-00866-7","url":null,"abstract":"Hakhamanesh Mostafavi recalls a landmark paper by Boyle et al. on the omnigenic model, which proposed that complex traits are influenced by thousands of genes across the genome, including many that are only indirectly related to a trait through regulatory networks.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 8","pages":"513-513"},"PeriodicalIF":52.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296057","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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