Pub Date : 2024-03-01DOI: 10.1038/s41576-024-00714-0
Kate E. Galloway
Kate Galloway highlights a paper by Kueh et al., who showed that the cell cycle indirectly influences concentrations of the transcription factor PU.1 to stabilize cell-fate trajectories in mice.
{"title":"Changes in cell-cycle rate drive diverging cell fates","authors":"Kate E. Galloway","doi":"10.1038/s41576-024-00714-0","DOIUrl":"10.1038/s41576-024-00714-0","url":null,"abstract":"Kate Galloway highlights a paper by Kueh et al., who showed that the cell cycle indirectly influences concentrations of the transcription factor PU.1 to stabilize cell-fate trajectories in mice.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 6","pages":"379-379"},"PeriodicalIF":42.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013035","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 : 2024-02-29DOI: 10.1038/s41576-024-00716-y
Hajk-Georg Drost
In this Journal Club, Hajk-Georg Drost highlights a recent study by Pavlopoulos et al. that organizes proteins at tree-of-life scale using massively parallel graph-based clustering.
{"title":"Unveiling the expanding protein universe of life","authors":"Hajk-Georg Drost","doi":"10.1038/s41576-024-00716-y","DOIUrl":"10.1038/s41576-024-00716-y","url":null,"abstract":"In this Journal Club, Hajk-Georg Drost highlights a recent study by Pavlopoulos et al. that organizes proteins at tree-of-life scale using massively parallel graph-based clustering.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 5","pages":"306-306"},"PeriodicalIF":42.7,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996915","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 : 2024-02-29DOI: 10.1038/s41576-024-00693-2
Michela Coan, Simon Haefliger, Samir Ounzain, Rory Johnson
RNA therapeutics (RNATx) aim to treat diseases, including cancer, by targeting or employing RNA molecules for therapeutic purposes. Amongst the most promising targets are long non-coding RNAs (lncRNAs), which regulate oncogenic molecular networks in a cell type-restricted manner. lncRNAs are distinct from protein-coding genes in important ways that increase their therapeutic potential yet also present hurdles to conventional clinical development. Advances in genome editing, oligonucleotide chemistry, multi-omics and RNA engineering are paving the way for efficient and cost-effective lncRNA-focused drug discovery pipelines. In this Review, we present the emerging field of lncRNA therapeutics for oncology, with emphasis on the unique strengths and challenges of lncRNAs within the broader RNATx framework. We outline the necessary steps for lncRNA therapeutics to deliver effective, durable, tolerable and personalized treatments for cancer. Therapeutics that target long non-coding RNAs (lncRNAs) are promising treatments for cancer. In this Review, the authors discuss how technological advances have helped improve drug discovery pipelines for lncRNAs and overview their strengths and challenges as oncological therapeutics.
{"title":"Targeting and engineering long non-coding RNAs for cancer therapy","authors":"Michela Coan, Simon Haefliger, Samir Ounzain, Rory Johnson","doi":"10.1038/s41576-024-00693-2","DOIUrl":"10.1038/s41576-024-00693-2","url":null,"abstract":"RNA therapeutics (RNATx) aim to treat diseases, including cancer, by targeting or employing RNA molecules for therapeutic purposes. Amongst the most promising targets are long non-coding RNAs (lncRNAs), which regulate oncogenic molecular networks in a cell type-restricted manner. lncRNAs are distinct from protein-coding genes in important ways that increase their therapeutic potential yet also present hurdles to conventional clinical development. Advances in genome editing, oligonucleotide chemistry, multi-omics and RNA engineering are paving the way for efficient and cost-effective lncRNA-focused drug discovery pipelines. In this Review, we present the emerging field of lncRNA therapeutics for oncology, with emphasis on the unique strengths and challenges of lncRNAs within the broader RNATx framework. We outline the necessary steps for lncRNA therapeutics to deliver effective, durable, tolerable and personalized treatments for cancer. Therapeutics that target long non-coding RNAs (lncRNAs) are promising treatments for cancer. In this Review, the authors discuss how technological advances have helped improve drug discovery pipelines for lncRNAs and overview their strengths and challenges as oncological therapeutics.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 8","pages":"578-595"},"PeriodicalIF":39.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996914","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 : 2024-02-27DOI: 10.1038/s41576-024-00713-1
Carl G. de Boer
Carl G. de Boer highlights a recent paper by Lim et al. on the importance low-affinity transcription factor-binding sites for determining organismal phenotypes.
Carl G. de Boer 重点介绍了 Lim 等人最近发表的一篇关于低亲和性转录因子结合位点对决定生物表型的重要性的论文。
{"title":"The continuum of transcription factor affinities","authors":"Carl G. de Boer","doi":"10.1038/s41576-024-00713-1","DOIUrl":"10.1038/s41576-024-00713-1","url":null,"abstract":"Carl G. de Boer highlights a recent paper by Lim et al. on the importance low-affinity transcription factor-binding sites for determining organismal phenotypes.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 6","pages":"378-378"},"PeriodicalIF":42.7,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139976934","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 : 2024-02-20DOI: 10.1038/s41576-024-00691-4
Mona Schreiber, Murukarthick Jayakodi, Nils Stein, Martin Mascher
Plant genome sequences catalogue genes and the genetic elements that regulate their expression. Such inventories further research aims as diverse as mapping the molecular basis of trait diversity in domesticated plants or inquiries into the origin of evolutionary innovations in flowering plants millions of years ago. The transformative technological progress of DNA sequencing in the past two decades has enabled researchers to sequence ever more genomes with greater ease. Pangenomes — complete sequences of multiple individuals of a species or higher taxonomic unit — have now entered the geneticists’ toolkit. The genomes of crop plants and their wild relatives are being studied with translational applications in breeding in mind. But pangenomes are applicable also in ecological and evolutionary studies, as they help classify and monitor biodiversity across the tree of life, deepen our understanding of how plant species diverged and show how plants adapt to changing environments or new selection pressures exerted by human beings. Plant pangenomes have had a transformative impact on crop enhancement, biodiversity conservation and evolutionary research. This Review delves into the application of plant pangenomes for understanding trait diversity, aiding breeding, biodiversity classification and monitoring, and illuminating evolutionary innovations.
{"title":"Plant pangenomes for crop improvement, biodiversity and evolution","authors":"Mona Schreiber, Murukarthick Jayakodi, Nils Stein, Martin Mascher","doi":"10.1038/s41576-024-00691-4","DOIUrl":"10.1038/s41576-024-00691-4","url":null,"abstract":"Plant genome sequences catalogue genes and the genetic elements that regulate their expression. Such inventories further research aims as diverse as mapping the molecular basis of trait diversity in domesticated plants or inquiries into the origin of evolutionary innovations in flowering plants millions of years ago. The transformative technological progress of DNA sequencing in the past two decades has enabled researchers to sequence ever more genomes with greater ease. Pangenomes — complete sequences of multiple individuals of a species or higher taxonomic unit — have now entered the geneticists’ toolkit. The genomes of crop plants and their wild relatives are being studied with translational applications in breeding in mind. But pangenomes are applicable also in ecological and evolutionary studies, as they help classify and monitor biodiversity across the tree of life, deepen our understanding of how plant species diverged and show how plants adapt to changing environments or new selection pressures exerted by human beings. Plant pangenomes have had a transformative impact on crop enhancement, biodiversity conservation and evolutionary research. This Review delves into the application of plant pangenomes for understanding trait diversity, aiding breeding, biodiversity classification and monitoring, and illuminating evolutionary innovations.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 8","pages":"563-577"},"PeriodicalIF":39.1,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913143","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 : 2024-02-19DOI: 10.1038/s41576-024-00699-w
Michaela Holzem, Michael Boutros, Thomas W. Holstein
The Wnt signal transduction pathway has essential roles in the formation of the primary body axis during development, cellular differentiation and tissue homeostasis. This animal-specific pathway has been studied extensively in contexts ranging from developmental biology to medicine for more than 40 years. Despite its physiological importance, an understanding of the evolutionary origin and primary function of Wnt signalling has begun to emerge only recently. Recent studies on very basal metazoan species have shown high levels of conservation of components of both canonical and non-canonical Wnt signalling pathways. Furthermore, some pathway proteins have been described also in non-animal species, suggesting that recruitment and functional adaptation of these factors has occurred in metazoans. In this Review, we summarize the current state of research regarding the evolutionary origin of Wnt signalling, its ancestral function and the characteristics of the primal Wnt ligand, with emphasis on the importance of genomic studies in various pre-metazoan and basal metazoan species. This Review discusses the evolutionary origin of Wnt signalling, its ancestral function and the characteristics of the primal Wnt ligand. It emphasizes the importance of genomic studies in pre-metazoan and basal metazoan species to understanding the evolutionary origin of signalling pathways.
{"title":"The origin and evolution of Wnt signalling","authors":"Michaela Holzem, Michael Boutros, Thomas W. Holstein","doi":"10.1038/s41576-024-00699-w","DOIUrl":"10.1038/s41576-024-00699-w","url":null,"abstract":"The Wnt signal transduction pathway has essential roles in the formation of the primary body axis during development, cellular differentiation and tissue homeostasis. This animal-specific pathway has been studied extensively in contexts ranging from developmental biology to medicine for more than 40 years. Despite its physiological importance, an understanding of the evolutionary origin and primary function of Wnt signalling has begun to emerge only recently. Recent studies on very basal metazoan species have shown high levels of conservation of components of both canonical and non-canonical Wnt signalling pathways. Furthermore, some pathway proteins have been described also in non-animal species, suggesting that recruitment and functional adaptation of these factors has occurred in metazoans. In this Review, we summarize the current state of research regarding the evolutionary origin of Wnt signalling, its ancestral function and the characteristics of the primal Wnt ligand, with emphasis on the importance of genomic studies in various pre-metazoan and basal metazoan species. This Review discusses the evolutionary origin of Wnt signalling, its ancestral function and the characteristics of the primal Wnt ligand. It emphasizes the importance of genomic studies in pre-metazoan and basal metazoan species to understanding the evolutionary origin of signalling pathways.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 7","pages":"500-512"},"PeriodicalIF":42.7,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906199","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 : 2024-02-16DOI: 10.1038/s41576-024-00692-3
Hope A. Tanudisastro, Ira W. Deveson, Harriet Dashnow, Daniel G. MacArthur
Short tandem repeats (STRs) are highly polymorphic sequences throughout the human genome that are composed of repeated copies of a 1–6-bp motif. Over 1 million variable STR loci are known, some of which regulate gene expression and influence complex traits, such as height. Moreover, variants in at least 60 STR loci cause genetic disorders, including Huntington disease and fragile X syndrome. Accurately identifying and genotyping STR variants is challenging, in particular mapping short reads to repetitive regions and inferring expanded repeat lengths. Recent advances in sequencing technology and computational tools for STR genotyping from sequencing data promise to help overcome this challenge and solve genetically unresolved cases and the ‘missing heritability’ of polygenic traits. Here, we compare STR genotyping methods, analytical tools and their applications to understand the effect of STR variation on health and disease. We identify emergent opportunities to refine genotyping and quality-control approaches as well as to integrate STRs into variant-calling workflows and large cohort analyses. This Review describes tools and approaches for characterizing short tandem repeats in the human genome from whole-genome sequencing data. Furthermore, the authors discuss how these recent developments have helped to better understand the effect of short tandem repeats on human health and disease.
{"title":"Sequencing and characterizing short tandem repeats in the human genome","authors":"Hope A. Tanudisastro, Ira W. Deveson, Harriet Dashnow, Daniel G. MacArthur","doi":"10.1038/s41576-024-00692-3","DOIUrl":"10.1038/s41576-024-00692-3","url":null,"abstract":"Short tandem repeats (STRs) are highly polymorphic sequences throughout the human genome that are composed of repeated copies of a 1–6-bp motif. Over 1 million variable STR loci are known, some of which regulate gene expression and influence complex traits, such as height. Moreover, variants in at least 60 STR loci cause genetic disorders, including Huntington disease and fragile X syndrome. Accurately identifying and genotyping STR variants is challenging, in particular mapping short reads to repetitive regions and inferring expanded repeat lengths. Recent advances in sequencing technology and computational tools for STR genotyping from sequencing data promise to help overcome this challenge and solve genetically unresolved cases and the ‘missing heritability’ of polygenic traits. Here, we compare STR genotyping methods, analytical tools and their applications to understand the effect of STR variation on health and disease. We identify emergent opportunities to refine genotyping and quality-control approaches as well as to integrate STRs into variant-calling workflows and large cohort analyses. This Review describes tools and approaches for characterizing short tandem repeats in the human genome from whole-genome sequencing data. Furthermore, the authors discuss how these recent developments have helped to better understand the effect of short tandem repeats on human health and disease.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 7","pages":"460-475"},"PeriodicalIF":42.7,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747110","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":"Fitness effects of mutations throughout evolution","authors":"Henry Ertl","doi":"10.1038/s41576-024-00707-z","DOIUrl":"10.1038/s41576-024-00707-z","url":null,"abstract":"A study in Science uses bacteria from the Long-Term Evolution Experiment to report on how fitness effects of mutations change through evolution.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 4","pages":"233-233"},"PeriodicalIF":42.7,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747109","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 : 2024-02-16DOI: 10.1038/s41576-024-00708-y
Henry Ertl
Lan et al. report a high-throughput method for single-cell sequencing of diverse microbial communities.
Lan 等人报告了一种对不同微生物群落进行单细胞测序的高通量方法。
{"title":"Single-cell sequencing of diverse microorganisms","authors":"Henry Ertl","doi":"10.1038/s41576-024-00708-y","DOIUrl":"10.1038/s41576-024-00708-y","url":null,"abstract":"Lan et al. report a high-throughput method for single-cell sequencing of diverse microbial communities.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 4","pages":"234-234"},"PeriodicalIF":42.7,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747111","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 : 2024-02-14DOI: 10.1038/s41576-024-00706-0
Michael Attwaters
A study in Nature describes how single-cell expression data can be used to understand gene regulatory landscapes in bacteria.
自然》杂志上的一项研究介绍了如何利用单细胞表达数据来了解细菌的基因调控图谱。
{"title":"A TRIP to understand gene regulation","authors":"Michael Attwaters","doi":"10.1038/s41576-024-00706-0","DOIUrl":"10.1038/s41576-024-00706-0","url":null,"abstract":"A study in Nature describes how single-cell expression data can be used to understand gene regulatory landscapes in bacteria.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"25 4","pages":"234-234"},"PeriodicalIF":42.7,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735692","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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