Pub Date : 2024-11-06DOI: 10.1016/j.gde.2024.102276
Sefali Patel , Wen Liu , Ravikumar K , Catherine McCormick , Yong Fan
Recent advances in immunotherapy have underscored the potential of harnessing the immune system to treat disorders associated with immune dysregulation, such as primary and secondary immunodeficiencies, cancer, transplantation rejection, and aging. Owing to the cellular and structural complexity and the dynamic nature of immune responses, engineering immune organoids that replicate the function and key features of their corresponding immune organs continues to be a formidable challenge. In this overview, we will discuss the recent progress in bioengineering organoids of key primary and secondary immune organs and tissues, focusing particularly on their contributions to the host’s immune system in animal models and highlighting their potential roles in regenerative medicine.
{"title":"Engineering immune organoids to regenerate host immune system","authors":"Sefali Patel , Wen Liu , Ravikumar K , Catherine McCormick , Yong Fan","doi":"10.1016/j.gde.2024.102276","DOIUrl":"10.1016/j.gde.2024.102276","url":null,"abstract":"<div><div>Recent advances in immunotherapy have underscored the potential of harnessing the immune system to treat disorders associated with immune dysregulation, such as primary and secondary immunodeficiencies, cancer, transplantation rejection, and aging. Owing to the cellular and structural complexity and the dynamic nature of immune responses, engineering immune organoids that replicate the function and key features of their corresponding immune organs continues to be a formidable challenge. In this overview, we will discuss the recent progress in bioengineering organoids of key primary and secondary immune organs and tissues, focusing particularly on their contributions to the host’s immune system in animal models and highlighting their potential roles in regenerative medicine.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102276"},"PeriodicalIF":3.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593216","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 : 2024-11-05DOI: 10.1016/j.gde.2024.102274
Charis Fountas, Tineke L Lenstra
Transcriptional bursting refers to the stochastic transition of a promoter between transcriptionally active and inactive states. This dynamic process is highly regulated by the dynamics of transcription factor binding to DNA, their interactions with coactivators, and the 3D interactions between promoters, condensates, and enhancers. In this mini-review, we discuss recent insights into the kinetics of transcription factors and cofactors in both simple and complex regulatory environments to understand their impact on transcriptional bursting. We examine the novel concept of transcription factor exchange and relate it to different cooperativity models. Finally, we discuss recent live-cell imaging studies on the regulation of transcriptional bursting by enhancers and transcriptional condensates.
转录猝发是指启动子在转录活跃和不活跃状态之间的随机转换。这一动态过程受到转录因子与 DNA 结合的动态、转录因子与辅助激活因子的相互作用以及启动子、凝聚子和增强子之间的三维相互作用的高度调控。在这篇微型综述中，我们将讨论转录因子和辅助因子在简单和复杂调控环境中的动力学最新见解，以了解它们对转录猝发的影响。我们研究了转录因子交换的新概念，并将其与不同的合作性模型联系起来。最后，我们讨论了最近关于增强子和转录凝聚物调控转录突变的活细胞成像研究。
{"title":"Better together: how cooperativity influences transcriptional bursting","authors":"Charis Fountas, Tineke L Lenstra","doi":"10.1016/j.gde.2024.102274","DOIUrl":"10.1016/j.gde.2024.102274","url":null,"abstract":"<div><div>Transcriptional bursting refers to the stochastic transition of a promoter between transcriptionally active and inactive states. This dynamic process is highly regulated by the dynamics of transcription factor binding to DNA, their interactions with coactivators, and the 3D interactions between promoters, condensates, and enhancers. In this mini-review, we discuss recent insights into the kinetics of transcription factors and cofactors in both simple and complex regulatory environments to understand their impact on transcriptional bursting. We examine the novel concept of transcription factor exchange and relate it to different cooperativity models. Finally, we discuss recent live-cell imaging studies on the regulation of transcriptional bursting by enhancers and transcriptional condensates.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102274"},"PeriodicalIF":3.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584729","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 : 2024-10-29DOI: 10.1016/j.gde.2024.102272
Jonathan C Schmok , Gene W Yeo
Alternative splicing (AS) plays a pivotal role in protein diversity and mRNA maturation. Programmable control of targeted AS events is of longstanding interest in RNA biology, promising correction of dysregulated splicing in disease and discovery of AS events. This review explores four main strategies for programmable splicing manipulation: (1) inhibiting splicing signals with antisense oligonucleotides (ASOs), exemplified by therapies approved by the U.S. Food and Drug Administration, (2) applying DNA-targeting clustered regularly interspaced short palindromic repeats systems to edit splicing signals, (3) using synthetic splicing factors, including synthetic proteins and ribonucleoproteins, inspired by natural RNA-binding proteins, and (4) guiding endogenous splicing machinery with bifunctional ASOs and engineered small nuclear RNAs. While ASOs remain clinically prominent, emerging technologies aim for broad, scalable, durable, and precise splicing modulation, holding promise for transformative advancements in RNA biology and therapeutic interventions.
替代剪接（AS）在蛋白质多样性和 mRNA 成熟中起着关键作用。可编程控制目标 AS 事件是 RNA 生物学长期关注的问题，有望纠正疾病中的剪接失调并发现 AS 事件。本综述探讨了可编程剪接操作的四种主要策略：（1）用反义寡核苷酸（ASO）抑制剪接信号，美国食品药品管理局批准的疗法就是一例；（2）用反义寡核苷酸抑制剪接信号，美国食品药品管理局批准的疗法是一例；（3）用反义寡核苷酸抑制剪接信号，美国食品药品管理局批准的疗法是一例；（4）用反义寡核苷酸抑制剪接信号，美国食品药品管理局批准的疗法是一例。美国食品和药物管理局批准的疗法就是一例；(2) 利用 DNA 靶向簇状规则间隔短回文重复序列系统编辑剪接信号；(3) 利用合成剪接因子，包括受天然 RNA 结合蛋白启发的合成蛋白和核糖核蛋白；(4) 利用双功能 ASO 和工程化小核 RNA 引导内源性剪接机制。虽然 ASO 在临床上仍很突出，但新兴技术旨在实现广泛、可扩展、持久和精确的剪接调控，有望在 RNA 生物学和治疗干预方面取得变革性进展。
{"title":"Strategies for programmable manipulation of alternative splicing","authors":"Jonathan C Schmok , Gene W Yeo","doi":"10.1016/j.gde.2024.102272","DOIUrl":"10.1016/j.gde.2024.102272","url":null,"abstract":"<div><div>Alternative splicing (AS) plays a pivotal role in protein diversity and mRNA maturation. Programmable control of targeted AS events is of longstanding interest in RNA biology, promising correction of dysregulated splicing in disease and discovery of AS events. This review explores four main strategies for programmable splicing manipulation: (1) inhibiting splicing signals with antisense oligonucleotides (ASOs), exemplified by therapies approved by the U.S. Food and Drug Administration, (2) applying DNA-targeting clustered regularly interspaced short palindromic repeats systems to edit splicing signals, (3) using synthetic splicing factors, including synthetic proteins and ribonucleoproteins, inspired by natural RNA-binding proteins, and (4) guiding endogenous splicing machinery with bifunctional ASOs and engineered small nuclear RNAs. While ASOs remain clinically prominent, emerging technologies aim for broad, scalable, durable, and precise splicing modulation, holding promise for transformative advancements in RNA biology and therapeutic interventions.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102272"},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548683","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 : 2024-10-24DOI: 10.1016/j.gde.2024.102271
François Fuks , Michael Kharas
{"title":"Editorial overview: Epitranscriptomics: Exploring a new frontier in health and disease","authors":"François Fuks , Michael Kharas","doi":"10.1016/j.gde.2024.102271","DOIUrl":"10.1016/j.gde.2024.102271","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102271"},"PeriodicalIF":3.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512329","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 : 2024-10-18DOI: 10.1016/j.gde.2024.102270
Amber Louwagie , Ly P Vu
Epitranscriptomics, the study of chemical modifications of RNA molecules, is increasingly recognized as an important component of gene expression regulation. While the majority of research has focused on N6-methyladenosine (m6A) RNA methylation on mRNAs, emerging evidence has revealed that the m6A modification extends beyond mRNAs to include chromatin-associated RNAs (caRNAs). CaRNAs constitute an important class of RNAs characterized by their interaction with the genome and epigenome. These features allow caRNAs to be actively involved in shaping genome organization. In this review, we bring into focus recent findings of the dynamic interactions between caRNAs and chromatin architecture and how RNA methylation impacts caRNAs’ function in this interplay. We highlight several enabling techniques, which were critical for genome-wide profiling of caRNAs and their modifications. Given the nascent stage of the field, we emphasize on the need to address critical gaps in study of these modifications in more relevant biological systems. Overall, these exciting progress have expanded the scope and reach of epitranscriptomics, unveiling new mechanisms that underpin the control of gene expression and cellular phenotypes, with potential therapeutic implications.
{"title":"Emerging interactions between RNA methylation and chromatin architecture","authors":"Amber Louwagie , Ly P Vu","doi":"10.1016/j.gde.2024.102270","DOIUrl":"10.1016/j.gde.2024.102270","url":null,"abstract":"<div><div>Epitranscriptomics, the study of chemical modifications of RNA molecules, is increasingly recognized as an important component of gene expression regulation. While the majority of research has focused on N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) RNA methylation on mRNAs, emerging evidence has revealed that the m<sup>6</sup>A modification extends beyond mRNAs to include chromatin-associated RNAs (caRNAs). CaRNAs constitute an important class of RNAs characterized by their interaction with the genome and epigenome. These features allow caRNAs to be actively involved in shaping genome organization. In this review, we bring into focus recent findings of the dynamic interactions between caRNAs and chromatin architecture and how RNA methylation impacts caRNAs’ function in this interplay. We highlight several enabling techniques, which were critical for genome-wide profiling of caRNAs and their modifications. Given the nascent stage of the field, we emphasize on the need to address critical gaps in study of these modifications in more relevant biological systems. Overall, these exciting progress have expanded the scope and reach of epitranscriptomics, unveiling new mechanisms that underpin the control of gene expression and cellular phenotypes, with potential therapeutic implications.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102270"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445597","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 : 2024-10-09DOI: 10.1016/j.gde.2024.102268
Anastasiia Bondarieva, Kikuë Tachibana
The totipotent one-cell embryo, or zygote, gives rise to all germ layers and extraembryonic tissues that culminate in the development of a new organism. A zygote is produced at fertilisation by the fusion of differentiated germ cells, egg and sperm. The chromatin of parental genomes is reprogrammed and spatially reorganised in the early embryo. The 3D chromatin organisation is established de novo after fertilisation by a cohesin-dependent mechanism of loop extrusion that forms chromatin loops and topologically associating domains (TADs). Strengthening of TAD insulation is concomitant with the transcriptional ‘awakening’ of the embryo known as zygotic genome activation (ZGA). Whether and how these processes are causally linked remains poorly understood. In this review, we discuss recent findings of 3D chromatin organisation in mammalian gametes and embryos and how these are potentially related to ZGA.
{"title":"Genome folding and zygotic genome activation in mammalian preimplantation embryos","authors":"Anastasiia Bondarieva, Kikuë Tachibana","doi":"10.1016/j.gde.2024.102268","DOIUrl":"10.1016/j.gde.2024.102268","url":null,"abstract":"<div><div>The totipotent one-cell embryo, or zygote, gives rise to all germ layers and extraembryonic tissues that culminate in the development of a new organism. A zygote is produced at fertilisation by the fusion of differentiated germ cells, egg and sperm. The chromatin of parental genomes is reprogrammed and spatially reorganised in the early embryo. The 3D chromatin organisation is established <em>de novo</em> after fertilisation by a cohesin-dependent mechanism of loop extrusion that forms chromatin loops and topologically associating domains (TADs). Strengthening of TAD insulation is concomitant with the transcriptional ‘awakening’ of the embryo known as zygotic genome activation (ZGA). Whether and how these processes are causally linked remains poorly understood. In this review, we discuss recent findings of 3D chromatin organisation in mammalian gametes and embryos and how these are potentially related to ZGA.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102268"},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394940","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 : 2024-10-08DOI: 10.1016/j.gde.2024.102267
Lidiia Tynianskaia , Michael Heide
The evolutionary expansion of the neocortex in the ape lineage is the basis for the development of higher cognitive abilities. However, the human brain has uniquely increased in size and degree of folding, forming an essential foundation for advanced cognitive functions. This raises the question: what factors distinguish humans from our closest living primate relatives, such as chimpanzees and bonobos, which exhibit comparatively constrained cognitive capabilities? In this review, we focus on recent studies examining (modern) human-specific genetic traits that influence neural progenitor cells, whose behavior and activity are crucial for shaping cortical morphology. We emphasize the role of human-specific genetic modifications in signaling pathways that enhance the abundance of apical and basal progenitors, as well as the importance of basal progenitor metabolism in their proliferation in human. Additionally, we discuss how changes in neuron morphology contribute to the evolution of human cognition and provide our perspective on future directions in the field.
{"title":"Human-specific genetic hallmarks in neocortical development: focus on neural progenitors","authors":"Lidiia Tynianskaia , Michael Heide","doi":"10.1016/j.gde.2024.102267","DOIUrl":"10.1016/j.gde.2024.102267","url":null,"abstract":"<div><div>The evolutionary expansion of the neocortex in the ape lineage is the basis for the development of higher cognitive abilities. However, the human brain has uniquely increased in size and degree of folding, forming an essential foundation for advanced cognitive functions. This raises the question: what factors distinguish humans from our closest living primate relatives, such as chimpanzees and bonobos, which exhibit comparatively constrained cognitive capabilities? In this review, we focus on recent studies examining (modern) human-specific genetic traits that influence neural progenitor cells, whose behavior and activity are crucial for shaping cortical morphology. We emphasize the role of human-specific genetic modifications in signaling pathways that enhance the abundance of apical and basal progenitors, as well as the importance of basal progenitor metabolism in their proliferation in human. Additionally, we discuss how changes in neuron morphology contribute to the evolution of human cognition and provide our perspective on future directions in the field.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102267"},"PeriodicalIF":3.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394941","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 : 2024-10-04DOI: 10.1016/j.gde.2024.102269
Benjamin Prud’homme
The phenomenon of transvection, defined as a proximity-dependent interallelic interaction, has been observed in the context of complementation between mutant alleles for numerous Drosophila genes. Cases of transvection-like phenomena have also been observed in other species, including mammals. However, the potential contribution of transvection to wild-type gene regulation and the underlying mechanisms remain uncertain. Here, I review recent evidence demonstrating the relevance of transvection in physiological contexts. These findings suggest that transvection represents an additional layer of gene regulation that allows cells to fine-tune gene expression based on the proximity of homologous alleles. In addition, recent studies have measured the physical distance between interacting alleles, revealing unexpectedly large and variable distances. I will discuss how these distances are compatible with the ‘hub’ model of transcriptional regulation.
{"title":"The power of proximity: mechanisms and biological roles of transvection","authors":"Benjamin Prud’homme","doi":"10.1016/j.gde.2024.102269","DOIUrl":"10.1016/j.gde.2024.102269","url":null,"abstract":"<div><div>The phenomenon of transvection, defined as a proximity-dependent interallelic interaction, has been observed in the context of complementation between mutant alleles for numerous Drosophila genes. Cases of transvection-like phenomena have also been observed in other species, including mammals. However, the potential contribution of transvection to wild-type gene regulation and the underlying mechanisms remain uncertain. Here, I review recent evidence demonstrating the relevance of transvection in physiological contexts. These findings suggest that transvection represents an additional layer of gene regulation that allows cells to fine-tune gene expression based on the proximity of homologous alleles. In addition, recent studies have measured the physical distance between interacting alleles, revealing unexpectedly large and variable distances. I will discuss how these distances are compatible with the ‘hub’ model of transcriptional regulation.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102269"},"PeriodicalIF":3.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378517","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 : 2024-10-01DOI: 10.1016/j.gde.2024.102260
Baptiste Libé-Philippot , Franck Polleux , Pierre Vanderhaeghen
Animal speciation often involves novel behavioral features that rely on nervous system evolution. Human-specific brain features have been proposed to underlie specialized cognitive functions and to be linked, at least in part, to the evolution of synapses, neurons, and circuits of the cerebral cortex. Here, we review recent results showing that, while the human cortex is composed of a repertoire of cells that appears to be largely similar to the one found in other mammals, human cortical neurons do display specialized features at many levels, from gene expression to intrinsic physiological properties. The molecular mechanisms underlying human species-specific neuronal features remain largely unknown but implicate hominid-specific gene duplicates that encode novel molecular modifiers of neuronal function. The identification of human-specific genetic modifiers of neuronal function brings novel insights on brain evolution and function and, could also provide new insights on human species-specific vulnerabilities to brain disorders.
{"title":"If you please, draw me a neuron — linking evolutionary tinkering with human neuron evolution","authors":"Baptiste Libé-Philippot , Franck Polleux , Pierre Vanderhaeghen","doi":"10.1016/j.gde.2024.102260","DOIUrl":"10.1016/j.gde.2024.102260","url":null,"abstract":"<div><div>Animal speciation often involves novel behavioral features that rely on nervous system evolution. Human-specific brain features have been proposed to underlie specialized cognitive functions and to be linked, at least in part, to the evolution of synapses, neurons, and circuits of the cerebral cortex. Here, we review recent results showing that, while the human cortex is composed of a repertoire of cells that appears to be largely similar to the one found in other mammals, human cortical neurons do display specialized features at many levels, from gene expression to intrinsic physiological properties. The molecular mechanisms underlying human species-specific neuronal features remain largely unknown but implicate hominid-specific gene duplicates that encode novel molecular modifiers of neuronal function. The identification of human-specific genetic modifiers of neuronal function brings novel insights on brain evolution and function and, could also provide new insights on human species-specific vulnerabilities to brain disorders.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102260"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367300","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 : 2024-09-12DOI: 10.1016/j.gde.2024.102259
Marybeth Baumgartner , Yu Ji , James P Noonan
Uniquely human physical traits, such as an expanded cerebral cortex and changes in limb morphology that allow us to use tools and walk upright, are in part due to human-specific genetic changes that altered when, where, and how genes are expressed during development. Over 20 000 putative regulatory elements with potential human-specific functions have been discovered. Understanding how these elements contributed to human evolution requires identifying candidates most likely to have shaped human traits, then studying them in genetically modified animal models. Here, we review the progress and challenges in generating and studying such models and propose a pathway for advancing the field. Finally, we highlight that large-scale collaborations across multiple research domains are essential to decipher what makes us human.
{"title":"Reconstructing human-specific regulatory functions in model systems","authors":"Marybeth Baumgartner , Yu Ji , James P Noonan","doi":"10.1016/j.gde.2024.102259","DOIUrl":"10.1016/j.gde.2024.102259","url":null,"abstract":"<div><p>Uniquely human physical traits, such as an expanded cerebral cortex and changes in limb morphology that allow us to use tools and walk upright, are in part due to human-specific genetic changes that altered when, where, and how genes are expressed during development. Over 20 000 putative regulatory elements with potential human-specific functions have been discovered. Understanding how these elements contributed to human evolution requires identifying candidates most likely to have shaped human traits, then studying them in genetically modified animal models. Here, we review the progress and challenges in generating and studying such models and propose a pathway for advancing the field. Finally, we highlight that large-scale collaborations across multiple research domains are essential to decipher what makes us human.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102259"},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142171834","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}
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