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Multi-organelle-mediated mRNA localization in neurons and links to disease 神经元中多细胞器介导的mRNA定位及其与疾病的联系
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-03-07 DOI: 10.1016/j.gde.2025.102332
Vivienne Aline Bauer, Koppers Max
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.
脑功能需要神经元蛋白质组精确的时空调节。为了适应神经元远端前哨的蛋白质组，mrna被转运到神经突中进行局部翻译。这种mRNA定位和局部翻译对神经元功能和维持至关重要，这些过程的失调可能导致神经系统疾病。近年来，细胞器在调控树突和轴突的mRNA定位和局部翻译中发挥了关键作用。在这篇综述中，我们讨论了目前的证据和悬而未决的问题，这种细胞器介导的mRNA定位。我们强调了一个新兴的模型，其中多个细胞器创建和协调一个亚细胞微环境，可以支持精确的mRNA定位和选择性翻译。这似乎对维持细胞器和神经元的功能和健康至关重要，因为许多相关蛋白质的突变会导致各种神经系统疾病。
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引用次数: 0
Pluripotent stem cell–derived mesenchymal stem cells for therapeutic applications, developmental study, and cancer research 多能干细胞衍生的间充质干细胞用于治疗应用、发育研究和癌症研究
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-03-06 DOI: 10.1016/j.gde.2025.102327
Siyi Fu, Cheung K Yeung, Ren-He Xu
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, in vivo development, and application of ps-MSCs in cancer research. We will also discuss the perspectives and challenges of this relatively new source of MSCs.
人间充质干细胞（MSCs）因其在组织修复和再生中的重要作用而被广泛研究和应用于各种疾病的治疗。与从体细胞组织中分离的间充质干细胞相比，从人多能干细胞中分化出来的间充质干细胞具有类似的治疗效果，同时由于其来源细胞的无限和稳定供应，在质量控制和保证方面具有一定的优势。这使得ps-MSCs具有高度的药物性和治疗应用前景。本文主要介绍了ps-MSC的研究进展，重点介绍了ps-MSC的治疗特性、来源、体内发育及其在癌症研究中的应用。我们还将讨论这种相对较新的msc来源的前景和挑战。
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引用次数: 0
R-loop homeostasis in genome dynamics, gene expression and development 基因组动力学、基因表达和发育中的r环稳态
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-03-04 DOI: 10.1016/j.gde.2025.102325
Paula Aguilera , Andrés Aguilera
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.
r环是一把双刃剑，其功能作用在许多情况下对基因组完整性和基因表达构成威胁，并在细胞生理和发育中产生相关后果。许多因素通过在R-loop预防、解决或修复R-loop诱导的DNA损伤的水平上起作用来控制R-loop稳态。破译在不同压力下产生的r环的作用以及控制其稳态的过多过程对于评估其在细胞生理学中的影响及其与发育和疾病相关的生物学意义至关重要。在这里，我们回顾了过去两年的出版物，以帮助理解它们的生物学作用。
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引用次数: 0
Editorial overview: Peering into our history through a genetic lens: How advances in genetics are changing our understanding of human evolution 编辑概述：通过基因镜头窥视我们的历史：遗传学的进步如何改变我们对人类进化的理解
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-02-24 DOI: 10.1016/j.gde.2025.102326
Jason L Stein , Alex A Pollen
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引用次数: 0
Modeling forebrain regional development and connectivity by human brain organoids 用人脑类器官模拟前脑区域发育和连通性
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-02-20 DOI: 10.1016/j.gde.2025.102324
Mu Seog Choe , Cynthia Lo , In-Hyun Park
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.
前脑是现代人类存在的最重要的大脑结构之一，它容纳了独特的复杂的社会和认知功能，使我们的物种与众不同。因此，利用人类细胞对前脑发育进行建模对于我们理解人类发育的复杂性和设计相关疾病的治疗方法尤为重要。脑类器官领域的最新进展为研究前脑发育提供了前所未有的工具，从研究特定区域到探索前脑不同区域之间的束形成和连通性。在本文中，我们讨论了前脑的发育生物学和不同的方法来模拟其发展用类器官。
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引用次数: 0
Principles of long-range gene regulation 远程基因调控原理
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-02-13 DOI: 10.1016/j.gde.2025.102323
Sanyami Zunjarrao, Maria Cristina Gambetta
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.
基因启动子的转录在多细胞生物中以特定的时空模式发生，受基因组调控元件控制。调控元件和启动子之间的交流需要它们之间一定程度的物理接近；因此，大多数基因调控发生在基因组的局部。然而，最近的发现揭示了远程基因调控策略，通过克服线性基因组中调控元件和启动子之间的距离来增强它们之间的相互作用。这些新发现挑战了基因表达模式如何被控制的传统观点。本文综述了最近在果蝇和哺乳动物中报道的远程基因调控策略，为其机制和进化提供了新的见解。
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引用次数: 0
Exploring the connection between RNA splicing and intellectual disability 探索RNA剪接与智力缺陷之间的联系
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-02-08 DOI: 10.1016/j.gde.2025.102322
Anthony Caputo, Ashleigh E Schaffer
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.
智力残疾（ID）是一个广泛的诊断类别，包括认知能力受损的个体。虽然这些疾病有不同的病因，但新一代测序（NGS）的最新进展揭示了遗传病因的流行。特别是，影响RNA剪接的基因的种系突变日益成为ID疾病的常见原因。研究剪接和神经发育之间的功能关系是至关重要的，因为分子治疗需要对病理机制有细致入微的了解。在这篇综述中，我们首先总结了导致RNA剪接- id关系发现的趋势，然后讨论了RNA剪接在神经发育中的最新进展和未来的研究方向。最后，我们将讨论这些结果如何作为新兴疗法的基础。
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引用次数: 0
Decoding N6-methyladenosine’s dynamic role in stem cell fate and early embryo development: insights into RNA–chromatin interactions 解码n6 -甲基腺苷在干细胞命运和早期胚胎发育中的动态作用：rna -染色质相互作用的见解
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-02-04 DOI: 10.1016/j.gde.2025.102311
Lei Yang , Mingli Ma , Yawei Gao , Jun Liu
N6-methyladenosine (m6A), a reversible and dynamic RNA modification, plays pivotal roles in regulating stem cell pluripotency and early embryogenesis. Disruptions in m6A 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 m6A’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 m6A, highlighting its critical interplay with chromatin modifications, and explores its broader implications in stem cell biology and early embryonic development.
n6 -甲基腺苷（n6 - methylladenosine, m6A）是一种可逆的、动态的RNA修饰，在干细胞多能性和早期胚胎发生调控中起着关键作用。m6A稳态的破坏会导致严重的发育缺陷，损害诸如干细胞自我更新、谱系规范、卵母细胞成熟、合子基因组激活和受精后母体RNA降解等过程。除了在mRNA转运、稳定性和翻译中众所周知的作用外，最近的研究强调了m6A通过复杂的rna -染色质相互作用在转录调控中的关键作用，特别是涉及染色质相关调控rna （carrna）和反转录转座子rna。这篇综述深入研究了m6A的动态调控格局，强调了它与染色质修饰的关键相互作用，并探讨了其在干细胞生物学和早期胚胎发育中的广泛意义。
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引用次数: 0
Tile by tile: capturing the evolutionary mosaic of human conditions 一砖一瓦：捕捉人类环境的进化马赛克。
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-02-01 DOI: 10.1016/j.gde.2024.102297
Nicolò Caporale , Oliviero Leonardi , Carlo Emanuele Villa , Alessandro Vitriolo , Cedric Boeckx , Giuseppe Testa
The collection of Homo sapiens 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.
支持“人类状况”的智人解剖学特征的集合并不是在一个特定的时间和地点出现的，而是逐渐形成了一个网状的进化轨迹。最近对不同人类物种和种群之间的迁移模式和基因流动的重建绘制了一个马赛克，我们认为可以通过基因组比较和特定实验来阐明。在这里，我们首先回顾了可以通过描述各种领域的最新进展来实现这一实验努力的关键发现，强调了绘制当前人类神经多样性作为进化变化的解释性基础的重要性。然后，我们确定关键的细胞和分子观察。最后，考虑到大量可能的变异，我们将讨论的重点放在能够以一种与当代基因组和表型特征的惊人数量相兼容的方式对它们进行询问的技术上。
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引用次数: 0
Nuclear remodeling during cell fate transitions 细胞命运转变过程中的核重塑。
IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Current Opinion in Genetics & Development
Pub Date : 2025-02-01 DOI: 10.1016/j.gde.2024.102287
Xinyi Liu, Xiaoru Ling, Qi Tian, Zibin Huang, Junjun Ding
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.
全能干细胞是胚胎发育过程中最早的细胞，可以分化成完整的胚胎和胚胎外组织，这对理解发育和再生医学至关重要。本文综述了在多能性和全能性转变过程中核结构的动态重塑以及其他细胞命运转变过程的最新进展。此外，我们强调创新的实验和计算方法，阐明核结构和细胞命运决定之间的关系。通过整合这些见解，我们的目标是增强我们对核重塑如何影响全能性和其他细胞命运转变的理解，为未来在这一关键领域的研究铺平道路。
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引用次数: 0
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