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Novelty versus innovation of gene regulatory elements in human evolution and disease 人类进化和疾病中基因调控元件的新颖性与创新性
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-26 DOI: 10.1016/j.gde.2024.102279
Anushka Katikaneni , Craig B Lowe
It is not currently understood how much of human evolution is due to modifying existing functional elements in the genome versus forging novel elements from nonfunctional DNA. Many early experiments that aimed to assign genetic changes on the human lineage to their resulting phenotypic change have focused on mutations that modify existing elements. However, a number of recent studies have highlighted the potential ease and importance of forging novel gene regulatory elements from nonfunctional sequences on the human lineage. In this review, we distinguish gene regulatory element novelty from innovation. We propose definitions for these terms and emphasize their importance in studying the genetic basis of human uniqueness. We discuss why the forging of novel regulatory elements may have been less emphasized during the previous decades, and why novel regulatory elements are likely to play a significant role in both human adaptation and disease.
目前还不清楚人类的进化在多大程度上是由于修改了基因组中现有的功能元素，而不是从无功能的 DNA 中伪造出新的元素。许多旨在将人类血统中的基因变化归因于其导致的表型变化的早期实验，都集中在改变现有元素的突变上。然而，最近的一些研究强调了从人类血统的非功能序列中伪造新基因调控元件的潜在难度和重要性。在这篇综述中，我们将基因调控元件的新颖性与创新性区分开来。我们提出了这些术语的定义，并强调了它们在研究人类独特性遗传基础中的重要性。我们讨论了为什么新型调控元件的形成在过去几十年中可能不太受重视，以及为什么新型调控元件可能在人类适应和疾病中发挥重要作用。
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引用次数: 0
Circuit integration by transplanted human neurons 移植人体神经元的电路整合
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-23 DOI: 10.1016/j.gde.2024.102225
Qiang Yuan , Su-Chun Zhang
Transplantation-based cell therapy holds the potential to offer sustained and physiological repair for neurological diseases and injuries, which requires the integration of transplanted neurons into the neural circuits of the human brain. Recent studies involving transplantation of human pluripotent stem cell–derived neural progenitors into the brain of model animals reveal the remarkable capacity of grafted immature human neurons to mature, project axons in a long distance, and form both pre- and postsynaptic connections with host neurons, corresponding to functional recovery. Strikingly, this circuit integration depends largely on the identity of the transplanted cells and may be modified by external stimuli. This realization begs for enriched authentic target cells for transplantation and combination with rehabilitation for better therapeutic outcomes.
基于移植的细胞疗法有可能为神经系统疾病和损伤提供持续的生理修复，这需要将移植的神经元整合到人脑的神经回路中。最近的研究将人多能干细胞衍生的神经祖细胞移植到模式动物的大脑中，结果表明，移植的未成熟人类神经元具有显著的成熟能力，能长距离投射轴突，并与宿主神经元形成突触前和突触后连接，从而实现功能恢复。令人震惊的是，这种回路整合在很大程度上取决于移植细胞的特性，并可能因外部刺激而改变。这就要求为移植和康复结合提供富集的真实靶细胞，以取得更好的治疗效果。
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引用次数: 0
Unveiling the potential: implications of successful somatic cell-to-ganglion organoid reprogramming 揭示潜能：体细胞到神经节类器官成功重编程的意义
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-23 DOI: 10.1016/j.gde.2024.102227
Dongchang Xiao , Shuting Liu , Mengqing Xiang
Organoids have a wide range of potential applications in areas such as organ development, precision medicine, regenerative medicine, drug screening, disease modeling, and gene editing. Currently, most organoids are generated through three-dimensional (3D) in vitro culture of adult stem cells or pluripotent stem cells. However, this method of generating organoids still has several limitations and challenges, including complex manipulations, costly culturing materials, extended time requirements, and certain heterogeneity. Recently, we have found that fibroblasts, when overexpressing several key regulatory transcription factors, are able to directly and rapidly generate two types of ganglion organoids: sensory ganglion (SG) and autonomic ganglion (AG) organoids. They have structures and electrophysiological properties similar to those of endogenous organs in the body. Here, we provide a brief overview of organoid development, focusing on direct reprogramming of SG and AG organoids and their transplantation and regeneration. Finally, the advantages and prospects of direct reprogramming of organoids are discussed.
器官组织在器官发育、精准医学、再生医学、药物筛选、疾病建模和基因编辑等领域有着广泛的潜在应用。目前，大多数器官组织是通过成体干细胞或多能干细胞的三维体外培养生成的。然而，这种生成器官组织的方法仍存在一些局限性和挑战，包括操作复杂、培养材料昂贵、时间要求长以及一定的异质性。最近，我们发现成纤维细胞在过表达几种关键调控转录因子时，能够直接快速生成两种神经节类器官：感觉神经节（SG）和自主神经节（AG）类器官。它们具有与人体内生器官相似的结构和电生理特性。在此，我们将简要概述类器官的发展，重点介绍 SG 和 AG 类器官的直接重编程及其移植和再生。最后，我们讨论了类器官直接重编程的优势和前景。
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引用次数: 0
Control of cell fate upon transcription factor–driven cardiac reprogramming 转录因子驱动的心脏重编程对细胞命运的控制
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-23 DOI: 10.1016/j.gde.2024.102226
Huitong Shi , Brian M Spurlock , Jiandong Liu , Li Qian
Adult mammals are susceptible to substantial cardiomyocyte (CM) loss following various cardiac diseases due to the limited capacity of CM proliferation and regeneration. Recently, direct cardiac reprogramming, converting fibroblasts into induced CMs, has been achieved both in vitro and in vivo through forced expression of transcription factors (TFs). This review encapsulates the advancements made in enhancing reprogramming efficiency and underlying molecular mechanisms. It covers the optimization of TF-based reprogramming cocktails and in vivo delivery platform and recently identified regulators in enhancing reprogramming efficiency. In addition, we discuss recent insights into the molecular mechanisms of direct cardiac reprogramming from single-cell omics analyses. Finally, we briefly touch on remaining challenges and prospective direction of this field.
由于心肌细胞（CM）的增殖和再生能力有限，成年哺乳动物在患上各种心脏疾病后很容易出现大量心肌细胞（CM）丢失。最近，通过强制表达转录因子（TFs），在体外和体内实现了直接心脏重编程，将成纤维细胞转化为诱导型 CM。本综述概括了在提高重编程效率和潜在分子机制方面取得的进展。它涵盖了基于 TF 的重编程鸡尾酒和体内递送平台的优化，以及最近发现的提高重编程效率的调节因子。此外，我们还讨论了最近从单细胞组学分析中获得的有关心脏直接重编程分子机制的见解。最后，我们简要介绍了这一领域仍然面临的挑战和未来的发展方向。
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引用次数: 0
Genetic factors mediating long-range enhancer–promoter communication in mammalian development 哺乳动物发育过程中介导长程增强子-启动子通讯的遗传因素
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-22 DOI: 10.1016/j.gde.2024.102282
Grace Bower, Evgeny Z Kvon
Enhancers are remotely located noncoding DNA sequences that regulate gene expression in response to developmental, homeostatic, and environmental cues. Canonical short-range enhancers located <50 kb from their cognate promoters function by binding transcription factors, coactivators, and chromatin modifiers. In this review, we discuss recent evidence that medium-range (50–400 kb) and long-range (>400 kb) enhancers rely on additional mechanisms, including cohesin, CCCTC-binding factor, and high-affinity protein–protein interactions. These mechanisms are crucial for establishing the physical proximity and interaction between enhancers and their target promoters over extended genomic distances and ensuring robust gene activation during mammalian development. Future studies will be critical to unravel their prevalence and evolutionary significance across various genomic loci, cell types, and species.
增强子是位置偏远的非编码 DNA 序列，可调节基因表达，对发育、同源性和环境线索做出反应。典型的短程增强子位于 400 kb）增强子依赖于其他机制，包括凝聚素、CCCTC 结合因子和高亲和性蛋白-蛋白相互作用。这些机制对于在较长的基因组距离内建立增强子与其目标启动子之间的物理邻近性和相互作用以及确保哺乳动物发育过程中基因的稳健激活至关重要。未来的研究对于揭示它们在不同基因组位点、细胞类型和物种中的普遍性和进化意义至关重要。
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引用次数: 0
Editorial overview: Drivers, droplets, and deeds of nuclear genome organization 编辑综述：核基因组组织的驱动力、液滴和契约。
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-21 DOI: 10.1016/j.gde.2024.102281
Maya Capelson , Eda Yildirim
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引用次数: 0
Archaic hominin admixture and its consequences for modern humans 古人类混居及其对现代人类的影响。
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-21 DOI: 10.1016/j.gde.2024.102280
Debashree Tagore, Joshua M Akey
As anatomically modern humans dispersed out of Africa, they encountered and mated with now extinct hominins, including Neanderthals and Denisovans. It is now well established that all non-African individuals derive approximately 2% of their genome from Neanderthal ancestors and individuals of Melanesian and Australian aboriginal ancestry inherited an additional 2%–5% of their genomes from Denisovan ancestors. Attention has started to shift from documenting amounts of archaic admixture and identifying introgressed segments to understanding their molecular, phenotypic, and evolutionary consequences and refining models of human history. Here, we review recent insights into admixture between modern and archaic humans, emphasizing methodological innovations and the functional and phenotypic effects Neanderthal and Denisovan sequences have in contemporary individuals.
随着解剖学上的现代人走出非洲，他们遇到了现已灭绝的类人猿，包括尼安德特人和丹尼索瓦人，并与之交配。现在可以确定的是，所有非非洲人的基因组中约有 2% 来自尼安德特人的祖先，而美拉尼西亚人和澳大利亚原住民祖先的基因组中又有 2%-5% 来自丹尼索瓦人的祖先。人们的注意力已开始从记录古老混血的数量和识别导入片段转向了解其分子、表型和进化后果以及完善人类历史模型。在这里，我们回顾了最近对现代人与古人类之间的混杂的见解，强调了方法的创新以及尼安德特人和丹尼索瓦人序列在当代个体中的功能和表型效应。
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引用次数: 0
Cell–cell interactions between transplanted retinal organoid cells and recipient tissues 移植视网膜类器官细胞与受体组织之间的细胞间相互作用
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-15 DOI: 10.1016/j.gde.2024.102277
Patrick O Nnoromele , McKaily Adams , Annabelle Pan , Ying V Liu , Joyce Wang , Mandeep S Singh
The transplantation of human organoid-derived retinal cells is being studied as a potentially viable strategy to treat vision loss due to retinal degeneration. Experiments in animal models have demonstrated the feasibility of organoid-derived photoreceptor transplantation in various recipient contexts. In some cases, vision repair has been shown. However, recipient–donor cell–cell interactions are incompletely understood. This review briefly summarizes these interactions, categorizing them as synaptic structure formation, cellular component transfer, glial activation, immune cell infiltration, and cellular migration. Each of these interactions may affect the survival and functionality of the donor cells and, ultimately, their efficacy as a treatment substrate. Additionally, recipient characteristics, such as the cytoarchitecture of the retina and immune status, may also impact the type and frequency of cell–cell interactions. Despite the procedural challenges associated with culturing human retinal organoids and the technical difficulties in transplanting donor cells into the delicate recipient retina, transplantation of retinal organoid-derived cells is a promising tool for degenerative retinal disease treatment.
目前正在研究将人类器官衍生视网膜细胞移植作为治疗视网膜变性导致的视力丧失的一种潜在可行策略。动物模型实验证明，在不同的受体情况下，类器官衍生光感受器移植是可行的。在某些情况下，视力得到了修复。然而，人们对受体-供体细胞-细胞之间的相互作用还不完全了解。本综述简要总结了这些相互作用，将其分为突触结构形成、细胞成分转移、神经胶质活化、免疫细胞浸润和细胞迁移。每种相互作用都可能影响供体细胞的存活和功能，并最终影响其作为治疗基质的功效。此外，受体的特征，如视网膜的细胞结构和免疫状态，也可能影响细胞-细胞相互作用的类型和频率。尽管培养人类视网膜类器官在程序上存在挑战，而且将供体细胞移植到脆弱的受体视网膜上也存在技术困难，但移植视网膜类器官衍生细胞是治疗视网膜退行性疾病的一种很有前景的工具。
{"title":"Cell–cell interactions between transplanted retinal organoid cells and recipient tissues","authors":"Patrick O Nnoromele ,&nbsp;McKaily Adams ,&nbsp;Annabelle Pan ,&nbsp;Ying V Liu ,&nbsp;Joyce Wang ,&nbsp;Mandeep S Singh","doi":"10.1016/j.gde.2024.102277","DOIUrl":"10.1016/j.gde.2024.102277","url":null,"abstract":"<div><div>The transplantation of human organoid-derived retinal cells is being studied as a potentially viable strategy to treat vision loss due to retinal degeneration. Experiments in animal models have demonstrated the feasibility of organoid-derived photoreceptor transplantation in various recipient contexts. In some cases, vision repair has been shown. However, recipient–donor cell–cell interactions are incompletely understood. This review briefly summarizes these interactions, categorizing them as synaptic structure formation, cellular component transfer, glial activation, immune cell infiltration, and cellular migration. Each of these interactions may affect the survival and functionality of the donor cells and, ultimately, their efficacy as a treatment substrate. Additionally, recipient characteristics, such as the cytoarchitecture of the retina and immune status, may also impact the type and frequency of cell–cell interactions. Despite the procedural challenges associated with culturing human retinal organoids and the technical difficulties in transplanting donor cells into the delicate recipient retina, transplantation of retinal organoid-derived cells is a promising tool for degenerative retinal disease treatment.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102277"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644932","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
How our brains are built: emerging approaches to understand human-specific features 我们的大脑是如何构建的：了解人类特有特征的新方法。
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-15 DOI: 10.1016/j.gde.2024.102278
Nicole D Moss , Davoneshia Lollis , Debra L Silver
Understanding what makes us uniquely human is a long-standing question permeating fields from genomics, neuroscience, and developmental biology to medicine. The discovery of human-specific genomic sequences has enabled a new understanding of the molecular features of human brain evolution. Advances in sequencing, computational, and in vitro screening approaches collectively reveal new roles of uniquely human sequences in regulating gene expression. Here, we review the landscape of human-specific loci and describe how emerging technologies are being used to understand their molecular functions and impact on brain development. We describe current challenges in the field and the potential of integrating new hypotheses and approaches to propel our understanding of the human brain.
了解是什么使我们成为独特的人类是一个长期存在的问题，它贯穿于从基因组学、神经科学、发育生物学到医学的各个领域。人类特异基因组序列的发现使人们对人类大脑进化的分子特征有了新的认识。测序、计算和体外筛选方法的进步共同揭示了人类特有序列在调控基因表达方面的新作用。在此，我们回顾了人类特异性基因座的情况，并介绍了如何利用新兴技术来了解它们的分子功能及其对大脑发育的影响。我们描述了该领域目前面临的挑战，以及整合新假说和新方法以促进我们对人类大脑的了解的潜力。
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引用次数: 0
Diversity of human skin three-dimensional organotypic cultures 人体皮肤三维有机培养物的多样性。
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2024-11-12 DOI: 10.1016/j.gde.2024.102275
Yunlong Y Jia , Scott X Atwood
Recently, significant strides have been made in the development of high-fidelity skin organoids, encompassing techniques such as 3D bioprinting, skin-on-a-chip systems, and models derived from pluripotent stem cells (PSCs), replicating appendage structures and diverse skin cell types. Despite the emergence of these state-of-the-art skin engineering models, human organotypic cultures (OTCs), initially proposed in the 1970s, continue to reign as the predominant in vitro cultured three-dimensional skin model in the field of tissue engineering. This enduring prevalence is owed to their cost-effectiveness, straight forward setup, time efficiency, and faithful representation of native human skin. In this review, we systematically delineate recent advances in skin OTC models, aiming to inform future efforts to enhance in vitro skin model fidelity and reproducibility.
最近，高保真皮肤器官组织的开发取得了长足进步，包括三维生物打印、片上皮肤系统和多能干细胞（PSCs）衍生模型等技术，复制了附肢结构和多种皮肤细胞类型。尽管出现了这些最先进的皮肤工程模型，但最初于 20 世纪 70 年代提出的人类器官型培养物（OTC）仍是组织工程领域最主要的体外培养三维皮肤模型。之所以能长期占据主导地位，是因为其成本效益高、设置简单、时间效率高，而且能忠实再现原生人体皮肤。在这篇综述中，我们系统地介绍了皮肤 OTC 模型的最新进展，旨在为今后提高体外皮肤模型的保真度和可重复性提供参考。
{"title":"Diversity of human skin three-dimensional organotypic cultures","authors":"Yunlong Y Jia ,&nbsp;Scott X Atwood","doi":"10.1016/j.gde.2024.102275","DOIUrl":"10.1016/j.gde.2024.102275","url":null,"abstract":"<div><div>Recently, significant strides have been made in the development of high-fidelity skin organoids, encompassing techniques such as 3D bioprinting, skin-on-a-chip systems, and models derived from pluripotent stem cells (PSCs), replicating appendage structures and diverse skin cell types. Despite the emergence of these state-of-the-art skin engineering models, human organotypic cultures (OTCs), initially proposed in the 1970s, continue to reign as the predominant <em>in vitro</em> cultured three-dimensional skin model in the field of tissue engineering. This enduring prevalence is owed to their cost-effectiveness, straight forward setup, time efficiency, and faithful representation of native human skin. In this review, we systematically delineate recent advances in skin OTC models, aiming to inform future efforts to enhance <em>in vitro</em> skin model fidelity and reproducibility.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102275"},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632085","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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