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Current Opinion in Genetics & Development最新文献

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Molecular mechanisms of the specialization of human synapses in the neocortex 人类新皮层突触特化的分子机制
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-09-09 DOI: 10.1016/j.gde.2024.102258
{"title":"Molecular mechanisms of the specialization of human synapses in the neocortex","authors":"","doi":"10.1016/j.gde.2024.102258","DOIUrl":"10.1016/j.gde.2024.102258","url":null,"abstract":"<div><p>Synapses of the neocortex specialized during human evolution to develop over extended timescales, process vast amounts of information and increase connectivity, which is thought to underlie our advanced social and cognitive abilities. These features reflect species-specific regulations of neuron and synapse cell biology. However, despite growing understanding of the human genome and the brain transcriptome at the single-cell level, linking human-specific genetic changes to the specialization of human synapses has remained experimentally challenging. In this review, we describe recent progress in characterizing divergent morphofunctional and developmental properties of human synapses, and we discuss new insights into the underlying molecular mechanisms. We also highlight intersections between evolutionary innovations and disorder-related dysfunctions at the synapse.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24001072/pdfft?md5=ef039913beee7944234497d1dfe20f66&pid=1-s2.0-S0959437X24001072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164826","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
Exploiting the plasticity of cholangiocytes to repair the biliary tree 利用胆管细胞的可塑性修复胆道树
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-09-09 DOI: 10.1016/j.gde.2024.102257
{"title":"Exploiting the plasticity of cholangiocytes to repair the biliary tree","authors":"","doi":"10.1016/j.gde.2024.102257","DOIUrl":"10.1016/j.gde.2024.102257","url":null,"abstract":"<div><p>Cholangiocytes are the main cell type lining the epithelium of the biliary tree of the liver. This cell type has been implicated not only in diseases affecting the biliary tree but also in chronic liver diseases targeting other hepatic cells such as hepatocytes. However, the isolation and culture of cholangiocytes have been particularly arduous, thereby limiting the development of new therapies. The emergence of organoids has the potential to address in part this challenge. Indeed, cholangiocyte organoids can be established from both the intra- and extrahepatic regions of the biliary tree, providing an advantageous platform for disease modeling and mechanism investigations. Accordingly, recent studies on cholangiocyte organoids, together with the advent of single-cell -omics, have opened the field to exciting discoveries concerning the plastic nature of these cells and their capability to adapt to different environments and stimuli. This review will focus on describing how these plasticity properties could be exploited in regenerative medicine and cell-based therapy, opening new frontiers for treating disorders affecting the biliary tree and beyond.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24001060/pdfft?md5=9e6c6420fd11cc3e263f24c031cdf99d&pid=1-s2.0-S0959437X24001060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164765","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
Editorial overview: Breaking boundaries: new frontiers in chromatin regulation for cancer therapy 编辑综述：打破界限：用于癌症治疗的染色质调控新领域
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-09-03 DOI: 10.1016/j.gde.2024.102255
{"title":"Editorial overview: Breaking boundaries: new frontiers in chromatin regulation for cancer therapy","authors":"","doi":"10.1016/j.gde.2024.102255","DOIUrl":"10.1016/j.gde.2024.102255","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128245","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
Massively parallel approaches for characterizing noncoding functional variation in human evolution 用大规模并行方法描述人类进化中的非编码功能变异
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-08-31 DOI: 10.1016/j.gde.2024.102256
{"title":"Massively parallel approaches for characterizing noncoding functional variation in human evolution","authors":"","doi":"10.1016/j.gde.2024.102256","DOIUrl":"10.1016/j.gde.2024.102256","url":null,"abstract":"<div><p>The genetic differences underlying unique phenotypes in humans compared to our closest primate relatives have long remained a mystery. Similarly, the genetic basis of adaptations between human groups during our expansion across the globe is poorly characterized. Uncovering the downstream phenotypic consequences of these genetic variants has been difficult, as a substantial portion lies in noncoding regions, such as <em>cis</em>-regulatory elements (CREs). Here, we review recent high-throughput approaches to measure the functions of CREs and the impact of variation within them. CRISPR screens can directly perturb CREs in the genome to understand downstream impacts on gene expression and phenotypes, while massively parallel reporter assays can decipher the regulatory impact of sequence variants. Machine learning has begun to be able to predict regulatory function from sequence alone, further scaling our ability to characterize genome function. Applying these tools across diverse phenotypes, model systems, and ancestries is beginning to revolutionize our understanding of noncoding variation underlying human evolution.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097379","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
Advances in skeletal genomics research across tissues and cells 跨组织和细胞的骨骼基因组研究取得进展
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-08-23 DOI: 10.1016/j.gde.2024.102245
{"title":"Advances in skeletal genomics research across tissues and cells","authors":"","doi":"10.1016/j.gde.2024.102245","DOIUrl":"10.1016/j.gde.2024.102245","url":null,"abstract":"<div><p>Phenotypic variation within the skeleton has biological, behavioral, and biomedical functional implications for individuals and species. Thus, it is critical to understand how genomic, environmental, and mediating regulatory factors combine and interact to drive skeletal trait development and evolution. Recent research efforts to clarify these mechanisms have been made possible by expanded collections of genomic and phenotypic data from <em>in vivo</em> skeletal tissues, as well as the development of relevant <em>in vitro</em> skeletal cell culture systems. This review outlines this current work and recommends that continued exploration of this complexity should include an increased focus on how interactions between genomic and physiologically relevant contexts contribute to skeletal trait variation at population and evolutionary scales.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000947/pdfft?md5=dc8f4465356de6f5ec2b769754b11bbf&pid=1-s2.0-S0959437X24000947-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049351","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
Evolutionary innovations in the primate dopaminergic system 灵长类多巴胺能系统的进化创新
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-08-16 DOI: 10.1016/j.gde.2024.102236
{"title":"Evolutionary innovations in the primate dopaminergic system","authors":"","doi":"10.1016/j.gde.2024.102236","DOIUrl":"10.1016/j.gde.2024.102236","url":null,"abstract":"<div><p>The human brain has evolved unique capabilities compared to other vertebrates. The mechanistic basis of these derived traits remains a fundamental question in biology due to its relevance to the origin of our cognitive abilities and behavioral repertoire, as well as to human-specific aspects of neuropsychiatric and neurodegenerative diseases. Comparisons of the human brain to those of nonhuman primates and other mammals have revealed that differences in the neuromodulatory systems, especially in the dopaminergic system, may govern some of these behavioral and cognitive alterations, including increased vulnerability to certain brain disorders. In this review, we highlight and discuss recent findings of human- and primate-specific alterations of the dopaminergic system, focusing on differences in anatomy, circuitry, and molecular properties.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000856/pdfft?md5=c90354b2ea654feaf66231c0258bda15&pid=1-s2.0-S0959437X24000856-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992972","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
Factors that determine cell type–specific CTCF binding in health and disease 决定健康和疾病中细胞类型特异性 CTCF 结合的因素
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-08-13 DOI: 10.1016/j.gde.2024.102244
{"title":"Factors that determine cell type–specific CTCF binding in health and disease","authors":"","doi":"10.1016/j.gde.2024.102244","DOIUrl":"10.1016/j.gde.2024.102244","url":null,"abstract":"<div><p>A number of factors contribute to cell type–specific CTCF chromatin binding, but how they act in concert to determine binding stability and functionality has not been fully elucidated. In this review, we tie together different layers of regulation to provide a holistic view of what is known. What emerges from these studies is a multifaceted system in which DNA sequence, DNA and chromatin accessibility, and cell type–specific transcription factors together contribute to CTCF binding profile and function. We discuss these findings in the light of disease settings in which changes in the chromatin landscape and transcriptional programming can disrupt CTCF’s binding profile and involvement in looping.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141985087","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
Xenotransplantation — a shortcut to construct tissue complexity in organoids 异种移植--在器官组织中构建复杂组织的捷径
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-08-13 DOI: 10.1016/j.gde.2024.102243
{"title":"Xenotransplantation — a shortcut to construct tissue complexity in organoids","authors":"","doi":"10.1016/j.gde.2024.102243","DOIUrl":"10.1016/j.gde.2024.102243","url":null,"abstract":"<div><p>Our knowledge of human biology is mainly originated from studies using animal models. However, interspecies differences between human and model organisms may lead to imprecise extrapolation of results obtained from model organisms. Organoids are three-dimensional cell clusters derived from pluripotent or adult stem cells that self-organize into organ-like structures reminiscent of the cognate organ. The establishment of human organoids makes it possible to study organ or tissue pathophysiology that is specific to human beings. However, most organoids do not have organ-specific vasculature, neurons, and immune cells, hence limiting their utility in emulating complex pathophysiological phenotypes. Among the various approaches to address these limitations, xenotransplantation represents a promising ‘shortcut’. We will discuss recent advance in constructing tissue complexity in organoids, with a special focus on xenotransplantation.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978596","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
Deciphering the role of structural variation in human evolution: a functional perspective 解读结构变异在人类进化中的作用：功能视角。
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-08-08 DOI: 10.1016/j.gde.2024.102240
{"title":"Deciphering the role of structural variation in human evolution: a functional perspective","authors":"","doi":"10.1016/j.gde.2024.102240","DOIUrl":"10.1016/j.gde.2024.102240","url":null,"abstract":"<div><p>Advances in sequencing technologies have enabled the comparison of high-quality genomes of diverse primate species, revealing vast amounts of divergence due to structural variation. Given their large size, structural variants (SVs) can simultaneously alter the function and regulation of multiple genes. Studies estimate that collectively more than 3.5% of the genome is divergent in humans versus other great apes, impacting thousands of genes. Functional genomics and gene-editing tools in various model systems recently emerged as an exciting frontier — investigating the wide-ranging impacts of SVs on molecular, cellular, and systems-level phenotypes. This review examines existing research and identifies future directions to broaden our understanding of the functional roles of SVs on phenotypic innovations and diversity impacting uniquely human features, ranging from cognition to metabolic adaptations.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000893/pdfft?md5=fa24fdab79f82513633e9a56eff9dd35&pid=1-s2.0-S0959437X24000893-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914449","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
Human-specific genetic modifiers of cortical architecture and function 大脑皮层结构和功能的人类特异性遗传修饰因子
IF 3.7 2区 生物学
Current Opinion in Genetics & Development Pub Date : 2024-08-06 DOI: 10.1016/j.gde.2024.102241
{"title":"Human-specific genetic modifiers of cortical architecture and function","authors":"","doi":"10.1016/j.gde.2024.102241","DOIUrl":"10.1016/j.gde.2024.102241","url":null,"abstract":"<div><p>Evolution of the cerebral cortex is thought to have been critical for the emergence of our cognitive abilities. Major features of cortical evolution include increased neuron number and connectivity and altered morpho-electric properties of cortical neurons. Significant progress has been made in identifying human-specific genetic modifiers (HSGMs), some of which are involved in shaping these features of cortical architecture. But how did these evolutionary changes support the emergence of our cognitive abilities? Here, we highlight recent studies aimed at examining the impact of HSGMs on cortical circuit function and behavior. We also discuss the need for greater insight into the link between evolution of cortical architecture and the functional and computational properties of neuronal circuits, as we seek to provide a neurobiological foundation for human cognition.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903471","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
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