{"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}
{"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}
{"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}
{"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}
{"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}
{"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}
{"title":"Exploring the connection between RNA splicing and intellectual disability","authors":"Anthony Caputo, Ashleigh E Schaffer","doi":"10.1016/j.gde.2025.102322","DOIUrl":"10.1016/j.gde.2025.102322","url":null,"abstract":"<div><div>Intellectual disability (ID) is a broad diagnostic category that encompasses individuals with impaired cognitive ability. While these disorders have heterogeneous causes, recent developments in next-generation sequencing (NGS) are revealing the prevalence of genetic etiologies. In particular, germline mutations in genes that affect RNA splicing are increasingly common causes of ID disorders. Research to elucidate the functional relationship between splicing and neurodevelopment is critical since molecular therapeutics require a nuanced understanding of the pathological mechanism. In this review, we first summarize the trends that have led to the discovery of the RNA splicing–ID relationship, then discuss recent progress and future directions for research surrounding RNA splicing in neurodevelopment. Finally, we speak on how these results may serve as the foundation for burgeoning therapies.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102322"},"PeriodicalIF":3.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372310","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}
{"title":"Decoding N6-methyladenosine’s dynamic role in stem cell fate and early embryo development: insights into RNA–chromatin interactions","authors":"Lei Yang , Mingli Ma , Yawei Gao , Jun Liu","doi":"10.1016/j.gde.2025.102311","DOIUrl":"10.1016/j.gde.2025.102311","url":null,"abstract":"<div><div><em>N</em><sup>6</sup>-methyladenosine (m<sup>6</sup>A), a reversible and dynamic RNA modification, plays pivotal roles in regulating stem cell pluripotency and early embryogenesis. Disruptions in m<sup>6</sup>A homeostasis lead to profound developmental defects, impairing processes such as stem cell self-renewal, lineage specification, oocyte maturation, zygotic genome activation, and maternal RNA degradation after fertilization. Beyond its well-recognized roles in mRNA transport, stability, and translation, recent studies have highlighted m<sup>6</sup>A’s critical role in transcriptional regulation through intricate RNA–chromatin interactions, notably involving chromatin-associated regulatory RNAs (carRNAs) and retrotransposon RNAs. This review delves into the dynamic regulatory landscape of m<sup>6</sup>A, highlighting its critical interplay with chromatin modifications, and explores its broader implications in stem cell biology and early embryonic development.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102311"},"PeriodicalIF":3.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143168794","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}
Nicolò Caporale , Oliviero Leonardi , Carlo Emanuele Villa , Alessandro Vitriolo , Cedric Boeckx , Giuseppe Testa
{"title":"Tile by tile: capturing the evolutionary mosaic of human conditions","authors":"Nicolò Caporale , Oliviero Leonardi , Carlo Emanuele Villa , Alessandro Vitriolo , Cedric Boeckx , Giuseppe Testa","doi":"10.1016/j.gde.2024.102297","DOIUrl":"10.1016/j.gde.2024.102297","url":null,"abstract":"<div><div>The collection of <em>Homo sapiens</em> anatomical hallmarks hypothesized to support the ‘human condition’ did not appear at one specific time and place, but gradually, creating a reticulate evolutionary trajectory. The recent reconstruction of migration patterns and gene flows across different hominin species and populations draws a mosaic that we contend can be illuminated by genomic comparisons and specific experiments. Here, we first review key discoveries that could allow this experimental endeavor by describing recent advances in a variety of fields, stressing the importance of charting the current human neurodiversity as an interpretive substrate for evolutionary changes. Then, we identify key cellular and molecular observables. Finally, given the vast amount of possible variants, we focus the discussion on technologies that could allow their interrogation in a way that is compatible with the staggering amount of contemporary genomic and phenotypic characterization.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"90 ","pages":"Article 102297"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873355","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}
{"title":"Nuclear remodeling during cell fate transitions","authors":"Xinyi Liu, Xiaoru Ling, Qi Tian, Zibin Huang, Junjun Ding","doi":"10.1016/j.gde.2024.102287","DOIUrl":"10.1016/j.gde.2024.102287","url":null,"abstract":"<div><div>Totipotent stem cells, the earliest cells in embryonic development, can differentiate into complete embryos and extra-embryonic tissues, making them essential for understanding both development and regenerative medicine. This review examines recent advances in the dynamic remodeling of nuclear structures during the transition between totipotency and pluripotency, as well as other cell fate transition processes. Additionally, we highlight innovative experimental and computational methods that elucidate the relationship between nuclear architecture and cell fate decisions. By integrating these insights, we aim to enhance our understanding of how nuclear remodeling influences totipotency and other cell fate transitions, paving the way for future research in this critical field.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"90 ","pages":"Article 102287"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781759","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}