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Spatial metabolomics to unravel cellular metabolism
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-28 DOI: 10.1038/s41576-025-00817-2
Arafath K. Najumudeen, Johan Vande Voorde
{"title":"Spatial metabolomics to unravel cellular metabolism","authors":"Arafath K. Najumudeen, Johan Vande Voorde","doi":"10.1038/s41576-025-00817-2","DOIUrl":"https://doi.org/10.1038/s41576-025-00817-2","url":null,"abstract":"In this Tools of the Trade article, Arafath Najumudeen and Johan Vande Voorde showcase the potential of mass spectrometry imaging for spatial metabolomics by highlighting its application in cancer, revealing metabolic differences between cell populations in the tumour microenvironment.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"19 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049947","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 early days of transcriptome sequencing and functional genomics
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-28 DOI: 10.1038/s41576-025-00814-5
Ayako Suzuki
{"title":"The early days of transcriptome sequencing and functional genomics","authors":"Ayako Suzuki","doi":"10.1038/s41576-025-00814-5","DOIUrl":"https://doi.org/10.1038/s41576-025-00814-5","url":null,"abstract":"Ayako Suzuki recalls two papers published in the early 2000s by the Functional Annotation of the Mammalian Genome (FANTOM) consortium and the Full-Length Long Japan (FLJ) project, which provided reference catalogues of full-length transcripts in mice and humans, respectively.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"37 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055053","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
Cytoplasmic mRNA decay and quality control machineries in eukaryotes
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-27 DOI: 10.1038/s41576-024-00810-1
Megan E. Dowdle, Jens Lykke-Andersen
{"title":"Cytoplasmic mRNA decay and quality control machineries in eukaryotes","authors":"Megan E. Dowdle, Jens Lykke-Andersen","doi":"10.1038/s41576-024-00810-1","DOIUrl":"https://doi.org/10.1038/s41576-024-00810-1","url":null,"abstract":"<p>mRNA degradation pathways have key regulatory roles in gene expression. The intrinsic stability of mRNAs in the cytoplasm of eukaryotic cells varies widely in a gene- and isoform-dependent manner and can be regulated by cellular cues, such as kinase signalling, to control mRNA levels and spatiotemporal dynamics of gene expression. Moreover, specialized quality control pathways exist to rid cells of non-functional mRNAs produced by errors in mRNA processing or mRNA damage that negatively impact translation. Recent advances in structural, single-molecule and genome-wide methods have provided new insights into the central machineries that carry out mRNA turnover, the mechanisms by which mRNAs are targeted for degradation and the general principles that govern mRNA stability at a global level. This improved understanding of mRNA degradation in the cytoplasm of eukaryotic cells is finding practical applications in the design of therapeutic mRNAs.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"77 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044066","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 hidden diversity of tumours
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-27 DOI: 10.1038/s41576-025-00815-4
Mariana Boroni
{"title":"The hidden diversity of tumours","authors":"Mariana Boroni","doi":"10.1038/s41576-025-00815-4","DOIUrl":"https://doi.org/10.1038/s41576-025-00815-4","url":null,"abstract":"In this Journal Club, Mariana Boroni recalls a 2012 study by Gerlinger et al. that revealed the complex and branched evolution of cancer and challenged the prevailing view of linear tumour progression.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"49 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044166","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
Diversity and consequences of structural variation in the human genome 人类基因组结构变异的多样性和后果
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-21 DOI: 10.1038/s41576-024-00808-9
Ryan L. Collins, Michael E. Talkowski
{"title":"Diversity and consequences of structural variation in the human genome","authors":"Ryan L. Collins, Michael E. Talkowski","doi":"10.1038/s41576-024-00808-9","DOIUrl":"https://doi.org/10.1038/s41576-024-00808-9","url":null,"abstract":"<p>The biomedical community is increasingly invested in capturing all genetic variants across human genomes, interpreting their functional consequences and translating these findings to the clinic. A crucial component of this endeavour is the discovery and characterization of structural variants (SVs), which are ubiquitous in the human population, heterogeneous in their mutational processes, key substrates for evolution and adaptation, and profound drivers of human disease. The recent emergence of new technologies and the remarkable scale of sequence-based population studies have begun to crystalize our understanding of SVs as a mutational class and their widespread influence across phenotypes. In this Review, we summarize recent discoveries and new insights into SVs in the human genome in terms of their mutational patterns, population genetics, functional consequences, and impact on human traits and disease. We conclude by outlining three frontiers to be explored by the field over the next decade.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"46 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990632","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
Profiling the total transcriptome of single nuclei in archived samples with snRandom-seq 用snRandom-seq分析存档样本中单个细胞核的总转录组
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-17 DOI: 10.1038/s41576-025-00812-7
Ziye Xu, Yongcheng Wang
{"title":"Profiling the total transcriptome of single nuclei in archived samples with snRandom-seq","authors":"Ziye Xu, Yongcheng Wang","doi":"10.1038/s41576-025-00812-7","DOIUrl":"https://doi.org/10.1038/s41576-025-00812-7","url":null,"abstract":"In this Tools of the Trade article, Ziye Xu and Yongcheng Wang describe snRandom-seq, a high-throughput, high-sensitivity single-nucleus total RNA sequencing technology optimized for archived samples.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"37 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987227","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
Indirect recognition of pathogen virulence proteins to activate plant immune receptors 间接识别病原体毒力蛋白，激活植物免疫受体
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-15 DOI: 10.1038/s41576-025-00811-8
Xiu-Fang Xin
{"title":"Indirect recognition of pathogen virulence proteins to activate plant immune receptors","authors":"Xiu-Fang Xin","doi":"10.1038/s41576-025-00811-8","DOIUrl":"https://doi.org/10.1038/s41576-025-00811-8","url":null,"abstract":"Xiu-Fang Xin recalls several papers that described one of the most influential and widely accepted examples of indirect activation of nucleotide-binding, leucine-rich repeat receptors in plants.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"52 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981350","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
Epigenetic ageing clocks: statistical methods and emerging computational challenges 表观遗传老化时钟：统计方法和新出现的计算挑战
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-13 DOI: 10.1038/s41576-024-00807-w
Andrew E. Teschendorff, Steve Horvath
{"title":"Epigenetic ageing clocks: statistical methods and emerging computational challenges","authors":"Andrew E. Teschendorff, Steve Horvath","doi":"10.1038/s41576-024-00807-w","DOIUrl":"https://doi.org/10.1038/s41576-024-00807-w","url":null,"abstract":"<p>Over the past decade, epigenetic clocks have emerged as powerful machine learning tools, not only to estimate chronological and biological age but also to assess the efficacy of anti-ageing, cellular rejuvenation and disease-preventive interventions. However, many computational and statistical challenges remain that limit our understanding, interpretation and application of epigenetic clocks. Here, we review these computational challenges, focusing on interpretation, cell-type heterogeneity and emerging single-cell methods, aiming to provide guidelines for the rigorous construction of interpretable epigenetic clocks at cell-type and single-cell resolution.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"31 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967972","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
Epigenetics and individuality: from concepts to causality across timescales 表观遗传学和个性：从概念到跨越时间尺度的因果关系
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-09 DOI: 10.1038/s41576-024-00804-z
Amy K. Webster, Patrick C. Phillips
{"title":"Epigenetics and individuality: from concepts to causality across timescales","authors":"Amy K. Webster, Patrick C. Phillips","doi":"10.1038/s41576-024-00804-z","DOIUrl":"https://doi.org/10.1038/s41576-024-00804-z","url":null,"abstract":"<p>Traditionally, differences among individuals have been divided into genetic and environmental causes. However, both types of variation can underlie regulatory changes in gene expression — that is, epigenetic changes — that persist across cell divisions (developmental differentiation) and even across generations (transgenerational inheritance). Increasingly, epigenetic variation among individuals is recognized as an important factor in human diseases and ageing. Moreover, non-genetic inheritance can lead to evolutionary changes within populations that differ from those expected by genetic inheritance alone. Despite its importance, causally linking epigenetic variation to phenotypic differences across individuals has proven difficult, particularly when epigenetic variation operates independently of genetic variation. New genomic approaches are providing unprecedented opportunity to measure and perturb epigenetic variation, helping to elucidate the role of epigenetic variation in mediating the genotype–phenotype map. Here, we review studies that have advanced our understanding of how epigenetic variation contributes to phenotypic differences between individuals within and across generations, and provide a unifying framework that allows historical and mechanistic perspectives to more fully inform one another.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"223 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937628","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 therapeutic potential of circular RNAs 环状rna的治疗潜力
IF 42.7 1区 生物学
Nature Reviews Genetics Pub Date : 2025-01-09 DOI: 10.1038/s41576-024-00806-x
Eoghan O’Leary, Yanyi Jiang, Lasse S. Kristensen, Thomas B. Hansen, Jørgen Kjems
{"title":"The therapeutic potential of circular RNAs","authors":"Eoghan O’Leary, Yanyi Jiang, Lasse S. Kristensen, Thomas B. Hansen, Jørgen Kjems","doi":"10.1038/s41576-024-00806-x","DOIUrl":"https://doi.org/10.1038/s41576-024-00806-x","url":null,"abstract":"<p>Over the past decade, research into circular RNA (circRNA) has increased rapidly, and over the past few years, circRNA has emerged as a promising therapeutic platform. The regulatory functions of circRNAs, including their roles in templating protein translation and regulating protein and RNA functions, as well as their unique characteristics, such as increased stability and a favourable immunological profile compared with mRNAs, make them attractive candidates for RNA-based therapies. Here, we describe the properties of circRNAs, their therapeutic potential and technologies for their synthesis. We also discuss the prospects and challenges to be overcome to unlock the full potential of circRNAs as drugs.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"44 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936913","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
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