Pub Date : 2025-03-18DOI: 10.1016/j.gde.2025.102329
Longzhi Tan , X. Sunney Xie , Stavros Lomvardas
Olfactory receptor (OR) gene choice, the stable expression of one out of >2000 OR alleles by olfactory sensory neurons, constitutes a gene regulatory process that is driven by three-dimensional nuclear architecture. Moreover, the differentiation-dependent process that culminates in monogenic and monoallelic OR transcription represents a powerful demonstration of the rich mechanistic insight that single-cell genomics and multiomics can provide toward the understanding of a biological process. At this review, we describe the latest advances in the understanding of OR gene regulation and highlight important standing questions regarding the emerging specificity of ultra-long-range genomic interaction and the contribution of transcription and noncoding RNAs.
{"title":"Genomic snowflakes: how the uniqueness of DNA folding allows us to smell the chemical universe","authors":"Longzhi Tan , X. Sunney Xie , Stavros Lomvardas","doi":"10.1016/j.gde.2025.102329","DOIUrl":"10.1016/j.gde.2025.102329","url":null,"abstract":"<div><div>Olfactory receptor (OR) gene choice, the stable expression of one out of >2000 OR alleles by olfactory sensory neurons, constitutes a gene regulatory process that is driven by three-dimensional nuclear architecture. Moreover, the differentiation-dependent process that culminates in monogenic and monoallelic OR transcription represents a powerful demonstration of the rich mechanistic insight that single-cell genomics and multiomics can provide toward the understanding of a biological process. At this review, we describe the latest advances in the understanding of OR gene regulation and highlight important standing questions regarding the emerging specificity of ultra-long-range genomic interaction and the contribution of transcription and noncoding RNAs.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102329"},"PeriodicalIF":3.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-17DOI: 10.1016/j.gde.2025.102331
Raquel García-Vílchez, Diana Guallar
Transposable elements (TEs) are mobile elements, which have been crucial for mammalian genome evolution and function. Their activity, which influences genomic stability, gene expression and chromatin state, is tightly regulated by complex mechanisms. This review examines recent findings on TE regulation and the dynamics and connection during the ageing process. Here, we explore the interplay between chromatin state, DNA, RNA, and histone modifications in controlling TE activity, with a special emphasis in elucidating the emerging role of epitranscriptomic modifications in TE regulation. Additionally, we analyse the connection between TE activation and ageing, with the perspective for future research that could reveal novel targets for alleviating physiological and pathological ageing and age-related diseases.
{"title":"Interplay of transposable elements and ageing: epigenetic regulation and potential epitranscriptomic influence","authors":"Raquel García-Vílchez, Diana Guallar","doi":"10.1016/j.gde.2025.102331","DOIUrl":"10.1016/j.gde.2025.102331","url":null,"abstract":"<div><div>Transposable elements (TEs) are mobile elements, which have been crucial for mammalian genome evolution and function. Their activity, which influences genomic stability, gene expression and chromatin state, is tightly regulated by complex mechanisms. This review examines recent findings on TE regulation and the dynamics and connection during the ageing process. Here, we explore the interplay between chromatin state, DNA, RNA, and histone modifications in controlling TE activity, with a special emphasis in elucidating the emerging role of epitranscriptomic modifications in TE regulation. Additionally, we analyse the connection between TE activation and ageing, with the perspective for future research that could reveal novel targets for alleviating physiological and pathological ageing and age-related diseases.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102331"},"PeriodicalIF":3.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-12DOI: 10.1016/j.gde.2025.102330
Adriana PerezGrovas-Saltijeral, Joseph Stones, Oliver C Orji, Hala Shaker, Helen M Knight
RNA metabolism is fundamental to protein synthesis, degradation and transport of molecules. Methylation of RNA influences the processing of mRNA, noncoding RNA, tRNA and rRNA. Here, we review accumulating evidence that disruption to the RNA methylome impairs developmental processes and causes neurodevelopmental conditions. We first describe mutated RNA methylation effector protein genes that give rise to neurodevelopmental syndromes. We consider the biological processes thereby disrupted, including translational dynamics at cytoplasmic and mt-ribosomes, synaptic function, energy production and cellular stress. Finally, we discuss novel forms of methylated RNA, such as R-loops and circular RNAs, which may contribute to disease processes. These findings herald an exciting new era to brain research and highlight the significant potential of manipulating the RNA methylome as a therapeutic target in the treatment of neurodevelopmental disorders.
{"title":"Modification of the RNA methylome in neurodevelopmental disorders","authors":"Adriana PerezGrovas-Saltijeral, Joseph Stones, Oliver C Orji, Hala Shaker, Helen M Knight","doi":"10.1016/j.gde.2025.102330","DOIUrl":"10.1016/j.gde.2025.102330","url":null,"abstract":"<div><div>RNA metabolism is fundamental to protein synthesis, degradation and transport of molecules. Methylation of RNA influences the processing of mRNA, noncoding RNA, tRNA and rRNA. Here, we review accumulating evidence that disruption to the RNA methylome impairs developmental processes and causes neurodevelopmental conditions. We first describe mutated RNA methylation effector protein genes that give rise to neurodevelopmental syndromes. We consider the biological processes thereby disrupted, including translational dynamics at cytoplasmic and mt-ribosomes, synaptic function, energy production and cellular stress. Finally, we discuss novel forms of methylated RNA, such as R-loops and circular RNAs, which may contribute to disease processes. These findings herald an exciting new era to brain research and highlight the significant potential of manipulating the RNA methylome as a therapeutic target in the treatment of neurodevelopmental disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102330"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-12DOI: 10.1016/j.gde.2025.102328
Andrés H Cardona , Márcia M Peixoto , Tohn Borjigin , Thomas Gregor
The development of multicellular organisms relies on the precise coordination of molecular events across multiple spatial and temporal scales. Understanding how information flows from molecular interactions to cellular processes and tissue organization during development is crucial for explaining the remarkable reproducibility of complex organisms. This review explores how chromatin-encoded information is transduced from localized transcriptional events to global gene expression patterns, highlighting the challenge of bridging these scales. We discuss recent experimental findings and theoretical frameworks, emphasizing polymer physics as a tool for describing the relationship between chromatin structure and dynamics across scales. By integrating these perspectives, we aim to clarify how gene regulation is coordinated across levels of biological organization and suggest strategies for future experimental approaches.
{"title":"Bridging spatial and temporal scales of developmental gene regulation","authors":"Andrés H Cardona , Márcia M Peixoto , Tohn Borjigin , Thomas Gregor","doi":"10.1016/j.gde.2025.102328","DOIUrl":"10.1016/j.gde.2025.102328","url":null,"abstract":"<div><div>The development of multicellular organisms relies on the precise coordination of molecular events across multiple spatial and temporal scales. Understanding how information flows from molecular interactions to cellular processes and tissue organization during development is crucial for explaining the remarkable reproducibility of complex organisms. This review explores how chromatin-encoded information is transduced from localized transcriptional events to global gene expression patterns, highlighting the challenge of bridging these scales. We discuss recent experimental findings and theoretical frameworks, emphasizing polymer physics as a tool for describing the relationship between chromatin structure and dynamics across scales. By integrating these perspectives, we aim to clarify how gene regulation is coordinated across levels of biological organization and suggest strategies for future experimental approaches.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102328"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-07DOI: 10.1016/j.gde.2025.102332
Vivienne Aline Bauer, Koppers Max
Brain function requires precise spatiotemporal regulation of the neuronal proteome. To allow adaptation of the proteome in distal outposts of neurons, mRNAs are transported into neurites for localized translation. This mRNA localization and local translation is crucial for neuron function and maintenance, and dysregulation of these processes can contribute to neurological disease. Recently, organelles have emerged as key players in regulating mRNA localization and local translation in dendrites and axons. In this review, we discuss the current evidence and open questions for this organelle-mediated mRNA localization. We highlight an emerging model in which multiple organelles create and orchestrate a subcellular microenvironment that can support precise mRNA localization and selective translation. This seems essential for maintaining organellar and neuronal function and health, as mutations in many of the involved proteins lead to various neurological disorders.
{"title":"Multi-organelle-mediated mRNA localization in neurons and links to disease","authors":"Vivienne Aline Bauer, Koppers Max","doi":"10.1016/j.gde.2025.102332","DOIUrl":"10.1016/j.gde.2025.102332","url":null,"abstract":"<div><div>Brain function requires precise spatiotemporal regulation of the neuronal proteome. To allow adaptation of the proteome in distal outposts of neurons, mRNAs are transported into neurites for localized translation. This mRNA localization and local translation is crucial for neuron function and maintenance, and dysregulation of these processes can contribute to neurological disease. Recently, organelles have emerged as key players in regulating mRNA localization and local translation in dendrites and axons. In this review, we discuss the current evidence and open questions for this organelle-mediated mRNA localization. We highlight an emerging model in which multiple organelles create and orchestrate a subcellular microenvironment that can support precise mRNA localization and selective translation. This seems essential for maintaining organellar and neuronal function and health, as mutations in many of the involved proteins lead to various neurological disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102332"},"PeriodicalIF":3.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-06DOI: 10.1016/j.gde.2025.102327
Siyi Fu, Cheung K Yeung, Ren-He Xu
Human mesenchymal stem cells (MSCs) have been widely studied and applied for the treatment of various diseases due to their crucial role in tissue repair and regeneration. Compared to MSCs isolated from somatic tissues, MSCs differentiated from human pluripotent stem cells (ps-MSCs) have demonstrated similar therapeutic effects while possessing some advantages in quality control and assurance, given their unlimited and consistent supply of source cells. This makes ps-MSCs highly druggable and promising for therapeutic applications. In this minireview, we introduce the latest progress in ps-MSC research, focusing on the therapeutic properties, origin, in vivo development, and application of ps-MSCs in cancer research. We will also discuss the perspectives and challenges of this relatively new source of MSCs.
{"title":"Pluripotent stem cell–derived mesenchymal stem cells for therapeutic applications, developmental study, and cancer research","authors":"Siyi Fu, Cheung K Yeung, Ren-He Xu","doi":"10.1016/j.gde.2025.102327","DOIUrl":"10.1016/j.gde.2025.102327","url":null,"abstract":"<div><div>Human mesenchymal stem cells (MSCs) have been widely studied and applied for the treatment of various diseases due to their crucial role in tissue repair and regeneration. Compared to MSCs isolated from somatic tissues, MSCs differentiated from human pluripotent stem cells (ps-MSCs) have demonstrated similar therapeutic effects while possessing some advantages in quality control and assurance, given their unlimited and consistent supply of source cells. This makes ps-MSCs highly druggable and promising for therapeutic applications. In this minireview, we introduce the latest progress in ps-MSC research, focusing on the therapeutic properties, origin, <em>in vivo</em> development, and application of ps-MSCs in cancer research. We will also discuss the perspectives and challenges of this relatively new source of MSCs.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102327"},"PeriodicalIF":3.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-04DOI: 10.1016/j.gde.2025.102325
Paula Aguilera , Andrés Aguilera
R-loops are double-edge swords with functional roles that in many cases constitute a threat to genome integrity and gene expression with relevant consequences in cell physiology and development. A number of factors have evolved to control R-loop homeostasis by acting at the levels of R-loop prevention, resolution, or the repair of the R-loop-induced DNA lesion. Deciphering the role of R-loops generated under different stresses and the plethora of processes controlling their homeostasis has become crucial to evaluate their impact in cell physiology and the biological significance of their association with development and disease. Here, we review publications of the last 2 years that help understand their biological role.
{"title":"R-loop homeostasis in genome dynamics, gene expression and development","authors":"Paula Aguilera , Andrés Aguilera","doi":"10.1016/j.gde.2025.102325","DOIUrl":"10.1016/j.gde.2025.102325","url":null,"abstract":"<div><div>R-loops are double-edge swords with functional roles that in many cases constitute a threat to genome integrity and gene expression with relevant consequences in cell physiology and development. A number of factors have evolved to control R-loop homeostasis by acting at the levels of R-loop prevention, resolution, or the repair of the R-loop-induced DNA lesion. Deciphering the role of R-loops generated under different stresses and the plethora of processes controlling their homeostasis has become crucial to evaluate their impact in cell physiology and the biological significance of their association with development and disease. Here, we review publications of the last 2 years that help understand their biological role.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102325"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-24DOI: 10.1016/j.gde.2025.102326
Jason L Stein , Alex A Pollen
{"title":"Editorial overview: Peering into our history through a genetic lens: How advances in genetics are changing our understanding of human evolution","authors":"Jason L Stein , Alex A Pollen","doi":"10.1016/j.gde.2025.102326","DOIUrl":"10.1016/j.gde.2025.102326","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102326"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-20DOI: 10.1016/j.gde.2025.102324
Mu Seog Choe , Cynthia Lo , In-Hyun Park
The forebrain is one of the most important brain structures for modern human existence, which houses the uniquely sophisticated social and cognitive functions that distinguish our species. Therefore, modeling the forebrain development by using human cells is especially critical for our understanding of the intricacies of human development and devising treatments for related diseases. Recent advancements in brain organoid fields have offered unprecedented tools to investigate forebrain development from studies on specific regions to exploring tract formation and connectivity between different regions of the forebrain. In this review, we discuss the developmental biology of the forebrain and diverse methods for modeling its development by using organoids.
{"title":"Modeling forebrain regional development and connectivity by human brain organoids","authors":"Mu Seog Choe , Cynthia Lo , In-Hyun Park","doi":"10.1016/j.gde.2025.102324","DOIUrl":"10.1016/j.gde.2025.102324","url":null,"abstract":"<div><div>The forebrain is one of the most important brain structures for modern human existence, which houses the uniquely sophisticated social and cognitive functions that distinguish our species. Therefore, modeling the forebrain development by using human cells is especially critical for our understanding of the intricacies of human development and devising treatments for related diseases. Recent advancements in brain organoid fields have offered unprecedented tools to investigate forebrain development from studies on specific regions to exploring tract formation and connectivity between different regions of the forebrain. In this review, we discuss the developmental biology of the forebrain and diverse methods for modeling its development by using organoids.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102324"},"PeriodicalIF":3.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-13DOI: 10.1016/j.gde.2025.102323
Sanyami Zunjarrao, Maria Cristina Gambetta
Transcription from gene promoters occurs in specific spatiotemporal patterns in multicellular organisms, controlled by genomic regulatory elements. The communication between a regulatory element and a promoter requires a certain degree of physical proximity between them; hence, most gene regulation occurs locally in the genome. However, recent discoveries have revealed long-range gene regulation strategies that enhance interactions between regulatory elements and promoters by overcoming the distances between them in the linear genome. These new findings challenge the traditional view of how gene expression patterns are controlled. This review examines long-range gene regulation strategies recently reported in Drosophila and mammals, offering insights into their mechanisms and evolution.
{"title":"Principles of long-range gene regulation","authors":"Sanyami Zunjarrao, Maria Cristina Gambetta","doi":"10.1016/j.gde.2025.102323","DOIUrl":"10.1016/j.gde.2025.102323","url":null,"abstract":"<div><div>Transcription from gene promoters occurs in specific spatiotemporal patterns in multicellular organisms, controlled by genomic regulatory elements. The communication between a regulatory element and a promoter requires a certain degree of physical proximity between them; hence, most gene regulation occurs locally in the genome. However, recent discoveries have revealed long-range gene regulation strategies that enhance interactions between regulatory elements and promoters by overcoming the distances between them in the linear genome. These new findings challenge the traditional view of how gene expression patterns are controlled. This review examines long-range gene regulation strategies recently reported in Drosophila and mammals, offering insights into their mechanisms and evolution.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102323"},"PeriodicalIF":3.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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