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Current Opinion in Genetics & Development最新文献

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Molecular basis of cell fate plasticity — insights from the privileged cells 细胞命运可塑性的分子基础——来自特权细胞的见解
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-05-05 DOI: 10.1016/j.gde.2025.102354
Stephen Maxwell Scalf, Qiao Wu, Shangqin Guo
{"title":"Molecular basis of cell fate plasticity — insights from the privileged cells","authors":"Stephen Maxwell Scalf,&nbsp;Qiao Wu,&nbsp;Shangqin Guo","doi":"10.1016/j.gde.2025.102354","DOIUrl":"10.1016/j.gde.2025.102354","url":null,"abstract":"<div><div>In the post-Yamanaka era, the rolling balls on Waddington’s hilly landscape not only roll downward, but also go upward or sideways. This new-found mobility implies that the tantalizing somatic cell plasticity fueling regeneration, once only known to planarians and newts, might be sparking in the cells of mice and humans, if only we knew how to fully unlock it. The hope for ultimate regeneration was made even more tangible by the observations that partial reprogramming by the Yamanaka factors reverses many hallmarks of aging [76], even though the underlying mechanism remains unclear. We intend to revisit the milestones in the evolving understanding of cell fate plasticity and glean molecular insights from an unusual somatic cell state, the privileged cell state that reprograms in a manner defying the stochastic model. We synthesize our view of the molecular underpinning of cell fate plasticity, from which we speculate how to harness it for regeneration and rejuvenation. We propose that senescence, aging and malignancy represent distinct cell states with definable biochemical and biophysical parameters.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102354"},"PeriodicalIF":3.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906682","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}
引用次数: 0
Rewinding the clock: mechanisms of dedifferentiation 时钟倒转：去分化机制
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-30 DOI: 10.1016/j.gde.2025.102353
Amelie A Raz , Yukiko M Yamashita
{"title":"Rewinding the clock: mechanisms of dedifferentiation","authors":"Amelie A Raz ,&nbsp;Yukiko M Yamashita","doi":"10.1016/j.gde.2025.102353","DOIUrl":"10.1016/j.gde.2025.102353","url":null,"abstract":"<div><div>Adult stem cells maintain tissue homeostasis through the production of differentiating cells. Considerable recent work has identified that stem cells themselves are replaceable through the process of dedifferentiation. The capacity and mechanisms of dedifferentiation vary widely among species and organ contexts. However, some core features are commonly present. In this review, we summarize ‘hallmarks’ of dedifferentiation, including mechanisms for maintenance of potency, sensation of loss, and migration, and review the current understanding of dedifferentiation as a true replacement mechanism.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102353"},"PeriodicalIF":3.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890918","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}
引用次数: 0
Unlocking regeneration: how partial reprogramming resembles tissue healing 解锁再生：部分重编程如何类似于组织愈合
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-30 DOI: 10.1016/j.gde.2025.102351
Melissa T Adams, Heinrich Jasper, Lluc Mosteiro
{"title":"Unlocking regeneration: how partial reprogramming resembles tissue healing","authors":"Melissa T Adams,&nbsp;Heinrich Jasper,&nbsp;Lluc Mosteiro","doi":"10.1016/j.gde.2025.102351","DOIUrl":"10.1016/j.gde.2025.102351","url":null,"abstract":"<div><div>Partial reprogramming achieved by the transient expression of the transcription factors (TFs) Oct4, Sox2, Klf4 and C-Myc (abbreviated OSKM) can erase aging and damage features in cells, leading to increased healthspan, lifespan and tissue regeneration. Recent reports suggest that the mechanisms of partial reprogramming may share some similarities with natural dedifferentiation and regeneration. Both processes appear to involve the transient repression of somatic identity through the sequestration of somatic identity TFs to noncanonical sites, which are opened by the high expression of pioneer TFs, leading to transient dedifferentiation into a fetal-like state. Here, we review the reported benefits of partial reprogramming on tissue regeneration and propose a common mechanism of epigenetic remodeling with natural regeneration after tissue injury.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102351"},"PeriodicalIF":3.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890916","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}
引用次数: 0
The hidden costs of imperfection: transcription errors in protein aggregation diseases 不完美的隐性代价：蛋白质聚集性疾病中的转录错误
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-29 DOI: 10.1016/j.gde.2025.102350
Yingwo Sun, Marc Vermulst
{"title":"The hidden costs of imperfection: transcription errors in protein aggregation diseases","authors":"Yingwo Sun,&nbsp;Marc Vermulst","doi":"10.1016/j.gde.2025.102350","DOIUrl":"10.1016/j.gde.2025.102350","url":null,"abstract":"<div><div>At first glance, biological systems appear to operate with remarkable precision and order. Yet, closer examination reveals that this perfection is an illusion, biological processes are inherently prone to errors. Here, we describe recent evidence that indicates that errors that occur during transcription play an important role in neurological diseases. These errors, though transient, can have lasting consequences when they generate mutant proteins with amyloid or prion-like properties. Such proteins can seed aggregation cascades, converting wild-type counterparts into misfolded conformations, ultimately leading to toxic deposits seen in diseases like Alzheimer’s and amyotrophic lateral sclerosis. These observations help to paint a fuller picture of the origins of neurodegenerative diseases in aging humans and suggest a unified mechanism by which they may arise.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102350"},"PeriodicalIF":3.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881751","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}
引用次数: 0
Paternal effects on telomere integrity during the sperm-to-embryo transition 精子到胚胎转变过程中，父系对端粒完整性的影响
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-25 DOI: 10.1016/j.gde.2025.102348
Sung-Ya Lin , Mia T Levine
{"title":"Paternal effects on telomere integrity during the sperm-to-embryo transition","authors":"Sung-Ya Lin ,&nbsp;Mia T Levine","doi":"10.1016/j.gde.2025.102348","DOIUrl":"10.1016/j.gde.2025.102348","url":null,"abstract":"<div><div>Telomeres are essential nucleoprotein structures that preserve our terminal DNA sequence and protect chromosome ends from fusion. Our vast knowledge of telomeres comes almost entirely from studies of healthy and diseased somatic cells. However, building evidence suggests that the molecules and mechanisms required for telomere integrity in somatic cells are insufficient to preserve telomere integrity during the sperm-to-embryo transition. Here, we review this growing body of work on telomere ‘paternal effects’, wherein zygotic telomere integrity is determined not by the genotype of the zygote but instead by the genotype of the father. Direct inheritance of sperm-specific proteins establishes paternal telomere epigenetic identity, while direct inheritance of sperm telomere length contributes to telomere length inheritance. Together, these investigations of telomere integrity through the sperm-to-embryo transition reveal potent paternal effects on zygotic telomere functions, with implications for human infertility.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102348"},"PeriodicalIF":3.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868698","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}
引用次数: 0
From conservation to adaptation: understanding the synaptonemal complex’s evolutionary dynamics 从保守到适应：理解突触复合体的进化动力学
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-16 DOI: 10.1016/j.gde.2025.102349
Stefanie Williams, Robin Scott Hawley
{"title":"From conservation to adaptation: understanding the synaptonemal complex’s evolutionary dynamics","authors":"Stefanie Williams,&nbsp;Robin Scott Hawley","doi":"10.1016/j.gde.2025.102349","DOIUrl":"10.1016/j.gde.2025.102349","url":null,"abstract":"<div><div>The synaptonemal complex (SC) is structurally conserved across eukaryotes and is essential for a proper progression of meiosis. Despite this conservation, SC protein sequences diverge drastically. In this review, we explore findings on SC protein evolution, highlighting key differences and commonalities among lineages like the <em>Caenorhabditis</em> and the <em>Drosophila</em> genera. We further explore known cases where the SC and its proteins adopt novel functional roles and discuss why knowledge of these cases could be important for the study of canonical SC biology. The existing studies demonstrate that work on the evolutionary biology of SC proteins and functional studies in more diverse meiotic research organisms should play a major role in aiding our understanding of SC structure and functions.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"93 ","pages":"Article 102349"},"PeriodicalIF":3.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843881","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}
引用次数: 0
Remodeling, compartmentalization, and degradation: a trifecta for organelle quality control during gametogenesis 重塑、分隔和降解：配子发生过程中细胞器质量控制的三部曲
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-14 DOI: 10.1016/j.gde.2025.102347
Tianyao Xiao, Elçin Ünal
{"title":"Remodeling, compartmentalization, and degradation: a trifecta for organelle quality control during gametogenesis","authors":"Tianyao Xiao,&nbsp;Elçin Ünal","doi":"10.1016/j.gde.2025.102347","DOIUrl":"10.1016/j.gde.2025.102347","url":null,"abstract":"<div><div>The key to healthy offspring production lies in the accurate inheritance of components from progenitor germ cells during gametogenesis. Along with genetic material, precise regulation of organelle inheritance is vital for gamete health and embryonic development, especially in aged organisms, where organelle function declines and damage accumulates. In these cases, removing age-related organellar defects in precursor cells is crucial for successful reproduction. The single-celled organism <em>Saccharomyces cerevisiae</em> shares striking similarities with more complex organisms: like metazoan cells, yeast accumulate organelle damage with age, yet can still produce damage-free gametes with a reset lifespan. Recent studies show that organelles undergo significant reorganization during yeast gametogenesis, and similar remodeling occurs in metazoans, suggesting common strategies for maintaining gamete quality. This review summarizes organellar reorganization during gametogenesis in yeast and how it aids in clearing age-related cellular damage. We also explore organellar remodeling in multicellular organisms and discuss the potential mechanisms and biological benefits of meiotic organellar reshaping.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102347"},"PeriodicalIF":3.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829348","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}
引用次数: 0
No more nonsense: evaluating poison exons as therapeutic targets in neurodevelopmental disorders 没有更多的废话：评估毒性外显子作为神经发育障碍的治疗靶点
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-09 DOI: 10.1016/j.gde.2025.102346
Shreeya Bakshi, Lori L Isom
{"title":"No more nonsense: evaluating poison exons as therapeutic targets in neurodevelopmental disorders","authors":"Shreeya Bakshi,&nbsp;Lori L Isom","doi":"10.1016/j.gde.2025.102346","DOIUrl":"10.1016/j.gde.2025.102346","url":null,"abstract":"<div><div>Alternative splicing of pre-mRNA generates multiple transcripts from a single gene, contributing to transcriptomic diversity. Alternative splicing can result in inclusion of poison exons (PEs), which contain a premature stop codons (PTC) that target transcripts for nonsense-mediated decay (NMD). PE-containing transcripts are prevalent in the brain, where they can play roles in fine-tuning mRNA and protein levels. Antisense, or splice-switching, oligonucleotides (ASOs/SSOs) are used to target PEs to reduce their inclusion and treat neurodevelopmental disorders. ASOs/SSOs address the genetic causes of disease and are precision therapies that can provide a cure rather than only address disease symptoms. This review explores the role of PEs in the brain, therapeutic targeting of PEs, and current challenges in our understanding of PEs.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102346"},"PeriodicalIF":3.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799968","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}
引用次数: 0
R-loops in neurodegeneration 神经变性中的 R 环
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-08 DOI: 10.1016/j.gde.2025.102345
Chiara Beghѐ, Helena Harpham, Yasmine Barberic, Natalia Gromak
{"title":"R-loops in neurodegeneration","authors":"Chiara Beghѐ,&nbsp;Helena Harpham,&nbsp;Yasmine Barberic,&nbsp;Natalia Gromak","doi":"10.1016/j.gde.2025.102345","DOIUrl":"10.1016/j.gde.2025.102345","url":null,"abstract":"<div><div>Neurodegenerative diseases are associated with the progressive loss of neurons. R-loops are non-canonical nucleic acid structures formed during transcription and composed of an RNA/DNA hybrid and a displaced single-stranded DNA. Whilst R-loops are important regulators of cellular processes, they are also associated with the pathologies of multiple disorders, including repeat expansion, motor neuron, inflammatory and ageing diseases. In this review, we discuss how R-loops contribute to pathological mechanisms that underpin neurodegeneration. We highlight the role of R-loops in several hallmarks of neurodegenerative disorders, including RNA and DNA defects, DNA damage, protein aggregation, inflammation, mitochondrial dysfunction, and neuronal cell death. We also discuss the potential role of R-loops as therapeutic targets for neurodegenerative disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102345"},"PeriodicalIF":3.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790942","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}
引用次数: 0
Reshaping transcription and translation dynamics during the awakening of the zygotic genome 在合子基因组觉醒期间重塑转录和翻译动力学
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2025-04-05 DOI: 10.1016/j.gde.2025.102344
Louise Maillard , Pierre Bensidoun , Mounia Lagha
{"title":"Reshaping transcription and translation dynamics during the awakening of the zygotic genome","authors":"Louise Maillard ,&nbsp;Pierre Bensidoun ,&nbsp;Mounia Lagha","doi":"10.1016/j.gde.2025.102344","DOIUrl":"10.1016/j.gde.2025.102344","url":null,"abstract":"<div><div>During the oocyte-to-embryo transition, the transcriptome and proteome are dramatically reshaped. This transition entails a shift from maternally inherited mRNAs to newly synthesized transcripts, produced during the zygotic genome activation (ZGA). Furthermore, a crucial transcription and translation selectivity is required for early embryonic development. Studies across various model organisms have revealed conserved <em>cis-</em> and <em>trans-</em>regulatory mechanisms dictating the regimes by which mRNA and proteins are produced during this critical phase. In this article, we highlight recent technological and conceptual advances that deepen our understanding of how the tuning of both transcription and translation evolves during ZGA.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"92 ","pages":"Article 102344"},"PeriodicalIF":3.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776585","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}
引用次数: 0
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