Nature Reviews Genetics最新文献_第8页

Reactivation of retrotransposable elements is associated with environmental stress and ageing 逆转录转座元件的重新激活与环境压力和老化有关

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-04-02 DOI: 10.1038/s41576-025-00829-y

Francesco Della Valle, Pradeep Reddy, Alain Aguirre Vazquez, Juan Carlos Izpisua Belmonte

{"title":"Reactivation of retrotransposable elements is associated with environmental stress and ageing","authors":"Francesco Della Valle, Pradeep Reddy, Alain Aguirre Vazquez, Juan Carlos Izpisua Belmonte","doi":"10.1038/s41576-025-00829-y","DOIUrl":"10.1038/s41576-025-00829-y","url":null,"abstract":"Retrotransposable elements (RTEs) are interspersed repetitive sequences that represent a large portion of eukaryotic genomes. Ancestral expansions of RTEs directly contributed to the shaping of these genomes and to the evolution of different species, particularly mammals. RTE activity is tightly regulated by different epigenetic mechanisms but this control becomes compromised as cells age and RTEs are reactivated. This dysregulation of RTEs leads to perturbation of cell function and organ and organismal homeostasis, which drives ageing and age-related disease. Environmental stress is associated with both ageing-related characteristics and the epigenetic mechanisms that control RTE activity, with accumulating evidence indicating that RTE reactivation mediates the effects of environmental stressors on ageing onset and progression. A better understanding of how RTEs are reactivated and their subsequent biological roles may help the development of therapies against ageing-related phenotypes and diseases. In this Review, Della Valle et al. discuss the role of retrotransposable elements (RTEs) in the onset and progression of ageing and ageing-related disease, including evidence that environmental stressors act through RTEs to shift the trajectory towards unhealthy ageing.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 8","pages":"547-558"},"PeriodicalIF":52.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758392","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

Computational analysis of DNA methylation from long-read sequencing 长读序列DNA甲基化的计算分析

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-28 DOI: 10.1038/s41576-025-00822-5

Yilei Fu (, ), Winston Timp, Fritz J. Sedlazeck

{"title":"Computational analysis of DNA methylation from long-read sequencing","authors":"Yilei Fu \u0000 (, ), Winston Timp, Fritz J. Sedlazeck","doi":"10.1038/s41576-025-00822-5","DOIUrl":"10.1038/s41576-025-00822-5","url":null,"abstract":"DNA methylation is a critical epigenetic mechanism in numerous biological processes, including gene regulation, development, ageing and the onset of various diseases such as cancer. Studies of methylation are increasingly using single-molecule long-read sequencing technologies to simultaneously measure epigenetic states such as DNA methylation with genomic variation. These long-read data sets have spurred the continuous development of advanced computational methods to gain insights into the roles of methylation in regulating chromatin structure and gene regulation. In this Review, we discuss the computational methods for calling methylation signals, contrasting methylation between samples, analysing cell-type diversity and gaining additional genomic insights, and then further discuss the challenges and future perspectives of tool development for DNA methylation research. Long-read sequencing technologies can directly profile methylation modifications across the genome. In this Review, Fu et al. overview the long-read computational tools to identify and compare methylation signals, as well as tools that use these methylation signals to analyse cell-type diversity and gain additional genomic insights.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 9","pages":"620-634"},"PeriodicalIF":52.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723482","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

Transcriptomics in the era of long-read sequencing 长读序列时代的转录组学

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-28 DOI: 10.1038/s41576-025-00828-z

Carolina Monzó, Tianyuan Liu, Ana Conesa

{"title":"Transcriptomics in the era of long-read sequencing","authors":"Carolina Monzó, Tianyuan Liu, Ana Conesa","doi":"10.1038/s41576-025-00828-z","DOIUrl":"10.1038/s41576-025-00828-z","url":null,"abstract":"Transcriptome sequencing revolutionized the analysis of gene expression, providing an unbiased approach to gene detection and quantification that enabled the discovery of novel isoforms, alternative splicing events and fusion transcripts. However, although short-read sequencing technologies have surpassed the limited dynamic range of previous technologies such as microarrays, they have limitations, for example, in resolving full-length transcripts and complex isoforms. Over the past 5 years, long-read sequencing technologies have matured considerably, with improvements in instrumentation and analytical methods, enabling their application to RNA sequencing (RNA-seq). Benchmarking studies are beginning to identify the strengths and limitations of long-read RNA-seq, although there remains a need for comprehensive resources to guide newcomers through the intricacies of this approach. In this Review, we provide a comprehensive overview of the long-read RNA-seq workflow, from library preparation and sequencing challenges to core data processing, downstream analyses and emerging developments. We present an extensive inventory of experimental and analytical methods and discuss current challenges and prospects. Advances in long-read sequencing are driving the implementation of these technologies for transcriptome profiling. The authors provide a comprehensive guide to long-read RNA sequencing, including experimental and computational tools, current applications, challenges and opportunities.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 10","pages":"681-701"},"PeriodicalIF":52.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723240","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

The genesis of paleogenetics 古遗传学的成因

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-27 DOI: 10.1038/s41576-025-00835-0

Maanasa Raghavan

引用次数: 0

From genome to drug: the hidden story of diversity 从基因组到药物：隐藏的多样性故事

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-20 DOI: 10.1038/s41576-025-00833-2

Minoli Perera

引用次数: 0

Challenges and solutions to the sustainability of gene and cell therapies 基因和细胞疗法可持续性的挑战和解决方案

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-10 DOI: 10.1038/s41576-025-00827-0

Celeste Scotti, Alessandro Aiuti, Luigi Naldini

引用次数: 0

Adapting systems biology to address the complexity of human disease in the single-cell era 适应系统生物学，以解决单细胞时代人类疾病的复杂性

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-10 DOI: 10.1038/s41576-025-00821-6

David S. Fischer, Martin A. Villanueva, Peter S. Winter, Alex K. Shalek

{"title":"Adapting systems biology to address the complexity of human disease in the single-cell era","authors":"David S. Fischer, Martin A. Villanueva, Peter S. Winter, Alex K. Shalek","doi":"10.1038/s41576-025-00821-6","DOIUrl":"10.1038/s41576-025-00821-6","url":null,"abstract":"Systems biology aims to achieve holistic insights into the molecular workings of cellular systems through iterative loops of measurement, analysis and perturbation. This framework has had remarkable success in unicellular model organisms, and recent experimental and computational advances — from single-cell and spatial profiling to CRISPR genome editing and machine learning — have raised the exciting possibility of leveraging such strategies to prevent, diagnose and treat human diseases. However, adapting systems-inspired approaches to dissect human disease complexity is challenging, given that discrepancies between the biological features of human tissues and the experimental models typically used to probe function (which we term ‘translational distance’) can confound insight. Here we review how samples, measurements and analyses can be contextualized within overall multiscale human disease processes to mitigate data and representation gaps. We then examine ways to bridge the translational distance between systems-inspired human discovery loops and model system validation loops to empower precision interventions in the era of single-cell genomics. Differences between humans and experimental models create a translational gap that makes it difficult to extrapolate research findings. The authors review systems-focused approaches to identify and control the translational distance between a complex disease process being studied and the experimental model used for testing.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 8","pages":"514-531"},"PeriodicalIF":52.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582917","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

Integrating model systems and genomic insights to decipher mechanisms of cancer metastasis 整合模型系统和基因组的见解来破译癌症转移的机制

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-10 DOI: 10.1038/s41576-025-00825-2

Michelle M. Leung, Charles Swanton, Nicholas McGranahan

{"title":"Integrating model systems and genomic insights to decipher mechanisms of cancer metastasis","authors":"Michelle M. Leung, Charles Swanton, Nicholas McGranahan","doi":"10.1038/s41576-025-00825-2","DOIUrl":"10.1038/s41576-025-00825-2","url":null,"abstract":"Deciphering metastatic processes is crucial for understanding cancer progression and potential treatment options. Genetic studies of model systems engineered to mimic metastatic disease, including organoids, genetically engineered mice and human cell lines, have had an important role in shaping our understanding of the metastatic cascade and how it can be manipulated. More recently, advances in high-throughput sequencing have enabled human metastases to be studied at single-cell and single-nucleotide resolution, providing insights into metastatic evolution and phenotypes of both cancer cells and immune cells. However, human tissue studies are often correlative and descriptive, whereas experimental models are reductionistic by nature, meaning that individual results should be interpreted with caution. Crucially, these seemingly disparate branches of metastasis research can and should complement each other to strengthen and validate findings. Here we explore the synergies between model systems and sequencing studies and outline key areas that must be explored to improve our understanding of the metastatic process. This Review explores how experimental models of metastasis, such as mouse models and cell cultures, can complement the (multi)omics analysis of human metastasis samples, thereby filling knowledge gaps left by model studies and validating the findings from human sequencing data.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 7","pages":"494-505"},"PeriodicalIF":52.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582923","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

Progress in understanding the vertebrate segmentation clock 脊椎动物分割时钟的研究进展

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-04 DOI: 10.1038/s41576-025-00813-6

Akihiro Isomura, Ryoichiro Kageyama

{"title":"Progress in understanding the vertebrate segmentation clock","authors":"Akihiro Isomura, Ryoichiro Kageyama","doi":"10.1038/s41576-025-00813-6","DOIUrl":"10.1038/s41576-025-00813-6","url":null,"abstract":"The segmentation clock is a molecular oscillator that regulates the periodic formation of somites from the presomitic mesoderm during vertebrate embryogenesis. Synchronous oscillatory expression of a Hairy homologue or Hairy-related basic helix–loop–helix (bHLH) transcriptional repressor in presomitic mesoderm cells regulates periodic expression of downstream factors that control somite segmentation with a periodicity that varies across species. Although many of the key components of the clock have been identified and characterized, less is known about how the clock is synchronized across cells and how species-specific periodicity is achieved. Advances in live imaging, stem cell and organoid technologies, and synthetic approaches have started to uncover the detailed mechanisms underlying these aspects of somitogenesis, providing insight into how morphogenesis is coordinated in space and time during embryonic development. In this Review, Isomura and Kageyama discuss how advances in live imaging, stem cell technologies and synthetic approaches are providing insights into the mechanisms underlying synchronization and species-specific periodicity of the mammalian segmentation clock during somitogenesis.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 7","pages":"479-493"},"PeriodicalIF":52.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538296","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

Beyond the black box with biologically informed neural networks 超越黑盒子，拥有生物信息的神经网络

IF 52 1区生物学

Nature Reviews Genetics Pub Date : 2025-03-04 DOI: 10.1038/s41576-025-00826-1

David A. Selby, Maximilian Sprang, Jan Ewald, Sebastian J. Vollmer

引用次数: 0