Current Opinion in Genetics & Development最新文献

英文中文

Exploring the origin of the development: totipotent stem cells 探索发育的起源：全能干细胞

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-07-10 DOI: 10.1016/j.gde.2025.102377

Shiyu Li , Hui Shen , Bing Peng , Peng Du

As the origin of the development, a fertilized egg owns the ability to generate a whole new organism, including both embryonic and extraembryonic tissues, representing the highest developmental potency, totipotency. For more than 40 years, pluripotent stem cells, with differentiation potential weaker than that of totipotent cells, have been easily derived from inner cell mass and maintained in vitro. Until now, capturing totipotent stem cells is still challenging. Recently, the stable culture of mouse and human totipotent blastomere–like cells was achieved for the first time using spliceosomal repression. Subsequently, other methods, particularly epigenetic manipulation, have also succeeded in culturing mouse totipotent stem cells. These advancements provide an excellent system for studying early embryonic development and offer new possibilities for regenerative medicine. However, the in vitro culture of totipotent stem cells has only been recently realized, and much further exploration is needed in this field. This review aims to compare different totipotent stem cells and discuss their potential applications in regenerative medicine and disease modeling.

作为发育的起点，受精卵具有生成全新生物体的能力，包括胚胎组织和胚胎外组织，代表着最高的发育潜能，即全能性。40多年来，多能干细胞的分化潜力弱于全能细胞，很容易从内部细胞群中获得并在体外维持。到目前为止，获取全能干细胞仍然具有挑战性。最近，利用剪接体抑制首次实现了小鼠和人的全能卵裂球样细胞的稳定培养。随后，其他方法，特别是表观遗传操作，也成功地培养了小鼠全能干细胞。这些进展为研究早期胚胎发育提供了一个很好的系统，并为再生医学提供了新的可能性。然而，全能干细胞的体外培养只是最近才实现的，这一领域还需要进一步的探索。本文旨在比较不同的全能干细胞，并讨论它们在再生医学和疾病建模方面的潜在应用。

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引用次数: 0

A haystack in the needle: packaging sperm DNA in insects 针中的干草堆：包装昆虫的精子DNA

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-07-07 DOI: 10.1016/j.gde.2025.102378

Raphaëlle Dubruille , Béatrice Horard , Benjamin Loppin

The global replacement of nucleosomes with nonhistone chromosomal proteins during sperm differentiation is a widespread phenomenon in sexually reproducing animals. In mammals, for instance, sperm chromatin is essentially packaged with protamines, a type of sperm nuclear basic proteins (SNBPs). In contrast to vertebrates, where many taxa retain variable levels of histones in their sperm chromatin, insects seem to systematically eliminate histones during spermiogenesis. This diversity of sperm packaging across metazoa raises questions about the functional significance of the histone-to-protamine transition that occurs during spermiogenesis. Recent studies in Drosophila and other insects have shed light on the function of SNBPs in packaging ultracompact sperm DNA and preparing paternal chromosomes for their integration into the diploid zygote.

在精子分化过程中，核小体被非组蛋白染色体蛋白替代是有性生殖动物中普遍存在的现象。例如，在哺乳动物中，精子染色质本质上包裹着精蛋白，这是一种精子核碱性蛋白（snbp）。与脊椎动物不同，许多类群在其精子染色质中保留了不同水平的组蛋白，而昆虫似乎在精子发生过程中系统地消除了组蛋白。精子包装在后生动物中的多样性提出了关于精子发生过程中历史蛋白到鱼精蛋白转变的功能意义的问题。最近对果蝇和其他昆虫的研究揭示了snbp在包装超紧凑精子DNA和准备父本染色体整合到二倍体受精卵中的功能。

引用次数: 0

Mitochondrial curation for the next generation 下一代的线粒体管理

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-07-05 DOI: 10.1016/j.gde.2025.102376

Gregory C. Gundberg , Jeremy Nance

The mitochondrial genome (mtDNA) can accumulate deleterious mutations that lead to disease. Animals have evolved strategies to eliminate mtDNA mutations in the maternal germ line, increasing the likelihood that their progeny inherit healthy mitochondria. Here, we provide an overview of mitochondrial quality control in the germ line, focusing on recent findings in mammals, Drosophila, and C. elegans. We discuss three strategies for quality control: elimination of sperm mtDNA, which prevents transmission of paternal mtDNA to progeny; the genetic bottleneck, which reduces the effective number of mtDNAs in germ cells, potentially exposing mutations to selection; and purifying selection, which selects for healthier mtDNAs. Finally, we discuss outstanding questions in the field and technical advances needed to address them.

线粒体基因组（mtDNA）可以积累导致疾病的有害突变。动物已经进化出了消除母体生殖系mtDNA突变的策略，从而增加了后代遗传健康线粒体的可能性。在这里，我们提供了线粒体质量控制的生殖系的概述，集中在哺乳动物，果蝇和秀丽隐杆线虫的最新发现。我们讨论了三种质量控制策略：消除精子mtDNA，防止父本mtDNA传给后代；遗传瓶颈，它减少了生殖细胞中mtdna的有效数量，可能使突变暴露于选择；以及净化选择，选择更健康的mtdna。最后，我们讨论了该领域的突出问题以及解决这些问题所需的技术进步。

引用次数: 0

The HNRNPs and neurodevelopmental disorders HNRNPs与神经发育障碍

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-06-30 DOI: 10.1016/j.gde.2025.102371

Madelyn A Gillentine

The HNRNP gene family has long been investigated in neurodegenerative disorders and cancer. Over the last several years, multiple members of the gene family have been associated with neurodevelopmental disorders. To date, there are nine well-established HNRNP-related neurodevelopmental disorders (HNRNP-RNDDs), at least three that are actively being characterized, and several candidate genes with a small number of patients. Here, we review the over 1000 individuals in the literature and patient databases and describe the overall phenotypic spectra of the HNRNP-RNDDs. Furthermore, we discuss recent advances in understanding the pathomechanisms of the HNRNP-RNDDs and how that will impact future therapeutic development.

HNRNP基因家族在神经退行性疾病和癌症中的研究由来已久。在过去的几年里，该基因家族的多个成员与神经发育障碍有关。迄今为止，已有9种hnrnp相关的神经发育障碍（hnrnp - rndd），至少有3种正在被积极地表征，以及少数患者的几个候选基因。在这里，我们回顾了文献和患者数据库中的1000多个个体，并描述了hnrnp - rndd的总体表型谱。此外，我们讨论了了解hnrnp - rndd的病理机制的最新进展，以及这将如何影响未来的治疗发展。

引用次数: 0

Addressing missing context in regulatory variation across primate evolution 解决灵长类动物进化中调控变异缺失的背景

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-06-26 DOI: 10.1016/j.gde.2025.102374

Genevieve Housman , Audrey Arner , Amy Longtin , Christian Gagnon , Arun Durvasula , Amanda Lea

In primates, loci associated with adaptive trait variation often fall in noncoding regions. Understanding the mechanisms linking these regulatory variants to fitness-relevant phenotypes remains challenging but can be addressed using functional genomic data. However, such data are rarely generated at scale in nonhuman primates. When they are, only select tissues, cell types, developmental stages, and cellular environments are typically considered, despite growing appreciation that adaptive variants often exhibit context-dependent effects. In this review, we (1) discuss why context-dependent regulatory loci might be especially relevant for understanding adaptive evolution in primates, (2) explore challenges and emerging solutions for mapping such context-dependent variation, and (3) discuss the scientific questions these data could address. Filling these gaps will provide critical insights into evolutionary processes, human disease, and regulatory adaptation.

在灵长类动物中，与适应性性状变异相关的基因座通常位于非编码区。理解将这些调节变异与健康相关表型联系起来的机制仍然具有挑战性，但可以使用功能基因组数据来解决。然而，这种数据很少在非人类灵长类动物中大规模产生。尽管越来越多的人认识到适应性变异经常表现出环境依赖效应，但当它们存在时，通常只考虑特定的组织、细胞类型、发育阶段和细胞环境。在这篇综述中，我们(1)讨论了为什么环境依赖的调控位点可能与理解灵长类动物的适应性进化特别相关，(2)探讨了绘制这种环境依赖变异的挑战和新兴解决方案，(3)讨论了这些数据可以解决的科学问题。填补这些空白将为进化过程、人类疾病和调节适应提供关键的见解。

引用次数: 0

The Yin and Yang of replicative aging and rejuvenation 生殖衰老和返老还童的阴阳

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-06-23 DOI: 10.1016/j.gde.2025.102375

Wei-Han Lin , Aliaksandr Damenikan , Yves Barral

Budding yeast undergoes replicative aging through asymmetric cell divisions. Yeast mother cells progressively age as they generate successive daughter cells, until they ultimately die. However, their daughters are born rejuvenated, that is, most of them recover a full lifespan potential, with little impact of their mothers’ age at their birth. In this review, we will discuss recent findings regarding the mechanisms of replicative aging and rejuvenation. Based on these insights, we will also discuss which evolutionary forces may have presided over the emergence of aging in yeast. We suggest that aging and rejuvenation represent two adaptive strategies that each bring their own benefits.

出芽酵母通过不对称的细胞分裂进行复制老化。酵母母细胞在产生连续的子细胞的过程中逐渐衰老，直到最终死亡。然而，他们的女儿出生时充满活力，也就是说，她们中的大多数人恢复了完整的生命潜力，几乎没有受到母亲出生时年龄的影响。在这篇综述中，我们将讨论关于复制衰老和返老返老机制的最新发现。基于这些见解，我们还将讨论哪些进化力量可能主持了酵母衰老的出现。我们认为衰老和返老还老是两种适应性策略，它们各自带来好处。

引用次数: 0

NOVA1/2 genes and alternative splicing in neurodevelopment NOVA1/2基因与神经发育中的选择性剪接

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-06-23 DOI: 10.1016/j.gde.2025.102373

Amélie Piton

NOVA1 and NOVA2 are neuron-specific RNA-binding proteins essential for alternative splicing (AS), influencing neurodevelopment by regulating transcript diversity. These proteins recognize YCAY sequences on pre-mRNA, regulating exon inclusion or skipping, intron retention, and alternative polyadenylation. Despite their 75% sequence identity, NOVA1 and NOVA2 exhibit distinct spatiotemporal expression patterns and target specificities, with NOVA2 predominantly expressed in cortical regions and NOVA1 in the cerebellum and spinal cord. De novo truncating variants in NOVA2 are responsible for a severe neurodevelopmental disorder (NDD), characterized by intellectual developmental disorder, motor delay, autistic features, and corpus callosum hypoplasia. Loss of Nova2 in animal models results in brain development anomalies, such as corpus callosum agenesis in mice, which mirrors the human neurodevelopmental phenotype. If direct evidence remains limited, emerging data suggest that mutations in NOVA1 might also be involved in neurological disorders. The contribution of other mRNA-binding proteins to NDD further underscores the critical role of regulation of RNA processing in neurodevelopment. This review explores the diverse functions of NOVA proteins, their impact on AS during brain development, and their implications in brain disorders.

NOVA1和NOVA2是选择性剪接（AS）所必需的神经元特异性rna结合蛋白，通过调节转录物多样性影响神经发育。这些蛋白识别前mrna上的YCAY序列，调节外显子包含或跳跃，内含子保留和选择性聚腺苷化。尽管NOVA1和NOVA2的序列具有75%的同源性，但它们表现出不同的时空表达模式和靶向特异性，其中NOVA2主要表达于皮质区，而NOVA1主要表达于小脑和脊髓。NOVA2的从头截断变异可导致严重的神经发育障碍（NDD），其特征是智力发育障碍、运动迟缓、自闭症特征和胼胝体发育不全。动物模型中Nova2的缺失会导致大脑发育异常，如小鼠的胼胝体发育，这反映了人类神经发育表型。如果直接证据仍然有限，新出现的数据表明NOVA1的突变也可能与神经系统疾病有关。其他mrna结合蛋白对NDD的贡献进一步强调了RNA加工调控在神经发育中的关键作用。本文综述了NOVA蛋白的多种功能，它们在大脑发育过程中对AS的影响，以及它们在大脑疾病中的意义。

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引用次数: 0

Lineage-specific regulatory evolution: insights from massively parallel reporter assays 谱系特异性调控进化：来自大规模平行报告者分析的见解

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-06-20 DOI: 10.1016/j.gde.2025.102372

Ryder Easterlin , Nadav Ahituv

Lineage-specific genetic variants play a key role in evolutionary divergence, particularly through changes in cis-regulatory elements that fine-tune gene expression. Massively parallel reporter assays (MPRAs) provide a powerful approach to characterize these variants at scale. This review highlights how MPRAs have been used to study lineage-specific regulatory activity in enhancer elements, including human accelerated regions, human adaptive quickly evolving regions, and short human-specific conserved deletions. We discuss the effects of enhancer variation on traits distinguishing modern humans, archaic hominins, and primates, as well as how MPRAs disentangle cis- and trans-regulatory contributions to gene expression divergence. As MPRA technology advances, integrating it with CRISPR-based validation and artificial intelligence–driven predictions will further illuminate the role of lineage-specific regulatory evolution.

谱系特异性遗传变异在进化分化中起着关键作用，特别是通过顺式调控元件的变化来微调基因表达。大规模并行报告分析（MPRAs）提供了一种强大的方法来大规模地表征这些变体。这篇综述强调了MPRAs如何被用于研究增强子元件的谱系特异性调控活性，包括人类加速区、人类适应性快速进化区和人类特异性短保守缺失。我们讨论了增强子变异对区分现代人、古人类和灵长类动物的性状的影响，以及MPRAs如何理清顺式和反式调控对基因表达差异的贡献。随着MPRA技术的进步，将其与基于crispr的验证和人工智能驱动的预测相结合，将进一步阐明谱系特异性调控进化的作用。

引用次数: 0

Transposon persistence and control in germ cells 转座子在生殖细胞中的持久性和控制

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-06-18 DOI: 10.1016/j.gde.2025.102370

Lauren Tracy, Zhao Zhang

Transposons, or ‘jumping genes’, are ubiquitous genomic elements with the dual capacity to drive evolutionary innovation and disrupt genome integrity through gene mutation and DNA damage. Their activity is particularly significant in germline cells, which transmit genetic material to the next generation. Transposon activity in these cells embodies a delicate balance: while limited transposon activity can introduce genetic diversity and drive evolution, unchecked mobilization risks DNA damage, sterility, and loss of fitness. As ‘selfish genes’, transposons have evolved strategies to ensure their propagation without jeopardizing host survival. This intricate relationship raises compelling questions about how transposon activity is regulated to sustain both genome stability and evolutionary potential. In this review, we explore recent advances in understanding the small RNA pathway that represses transposons in germ cells, the Piwi-interacting RNA pathway. Furthermore, we highlight how transposons creatively bypass repression. These findings illuminate the dynamic interplay between hosts and transposons, offering deeper insights into genome evolution and preservation.

转座子，或“跳跃基因”，是普遍存在的基因组元素，具有驱动进化创新和通过基因突变和DNA损伤破坏基因组完整性的双重能力。它们的活性在生殖细胞中尤为显著，生殖细胞将遗传物质传递给下一代。这些细胞中的转座子活性体现了一种微妙的平衡：有限的转座子活性可以引入遗传多样性并推动进化，而不受控制的转座子活性可能会导致DNA损伤、不育和适应性丧失。作为“自私基因”，转座子进化出了一些策略，以确保它们的繁殖不会危及宿主的生存。这种复杂的关系提出了一个令人信服的问题，即转座子的活性是如何被调节以维持基因组的稳定性和进化潜力的。在这篇综述中，我们探讨了生殖细胞中抑制转座子的小RNA通路，即piwi相互作用RNA通路的最新进展。此外，我们强调转座子如何创造性地绕过抑制。这些发现阐明了宿主和转座子之间的动态相互作用，为基因组进化和保存提供了更深入的见解。

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引用次数: 0

Transcriptional adaptation: where mRNA decay meets genetic compensation 转录适应：mRNA衰变与遗传补偿

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-06-10 DOI: 10.1016/j.gde.2025.102369

Lara Falcucci , Brian Juvik , Didier YR Stainier

Nonsense-mediated mRNA decay (NMD) is a translation-coupled quality control mechanism that safeguards cells against faulty transcripts that could lead to truncated and potentially harmful proteins. However, we posit that there is another side to NMD: it does not just clear away defective transcripts, it also triggers a form of genetic compensation known as transcriptional adaptation (TA). This recently discovered cellular response operates independently of protein loss. Instead, mutant mRNA decay can lead to the upregulation of functional paralogs, thereby compensating for the loss of the mutated gene. Consequently, TA could play a prominent role in genotype-phenotype correlations in human genetic diseases.

无义介导的mRNA衰变（NMD）是一种翻译耦合的质量控制机制，可保护细胞免受可能导致截断和潜在有害蛋白质的错误转录。然而，我们假设NMD还有另一方面：它不仅清除有缺陷的转录本，它还触发一种称为转录适应（TA）的遗传补偿形式。这种最近发现的细胞反应独立于蛋白质损失而起作用。相反，突变的mRNA衰减可以导致功能类似物的上调，从而补偿突变基因的损失。因此，TA可能在人类遗传疾病的基因型-表型相关性中发挥重要作用。

引用次数: 0

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