Current Opinion in Genetics & Development最新文献

英文中文

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 : 2025-08-01 Epub 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 hidden costs of imperfection: transcription errors in protein aggregation diseases 不完美的隐性代价：蛋白质聚集性疾病中的转录错误

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-08-01 Epub Date: 2025-04-29 DOI: 10.1016/j.gde.2025.102350

Yingwo Sun, Marc Vermulst

At first glance, biological systems appear to operate with remarkable precision and order. Yet, closer examination reveals that this perfection is an illusion, biological processes are inherently prone to errors. Here, we describe recent evidence that indicates that errors that occur during transcription play an important role in neurological diseases. These errors, though transient, can have lasting consequences when they generate mutant proteins with amyloid or prion-like properties. Such proteins can seed aggregation cascades, converting wild-type counterparts into misfolded conformations, ultimately leading to toxic deposits seen in diseases like Alzheimer’s and amyotrophic lateral sclerosis. These observations help to paint a fuller picture of the origins of neurodegenerative diseases in aging humans and suggest a unified mechanism by which they may arise.

乍一看，生物系统的运作似乎非常精确和有序。然而，更仔细的研究表明，这种完美是一种错觉，生物过程天生就容易出错。在这里，我们描述了最近的证据，表明转录过程中发生的错误在神经系统疾病中起着重要作用。这些错误虽然是短暂的，但当它们产生具有淀粉样蛋白或朊病毒样特性的突变蛋白时，可能会产生持久的后果。这些蛋白质可以引发聚集级联反应，将野生型的对应物转化为错误折叠的构象，最终导致阿尔茨海默氏症和肌萎缩性侧索硬化症等疾病的毒性沉积。这些观察结果有助于更全面地描绘出老年人类神经退行性疾病的起源，并提出了它们可能产生的统一机制。

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Recent advances in interspecies chimeras and organogenesis 种间嵌合和器官发生的最新进展

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-08-01 Epub Date: 2025-06-04 DOI: 10.1016/j.gde.2025.102368

Jia Huang , Bingbing He , Jun Wu

Interspecies chimeras have served as a crucial tool for understanding the mechanisms of tissue regeneration and repair, offering promising potential to address the global organ shortage crisis. Through a technique known as interspecies blastocyst complementation, researchers can cultivate tissues and organs of one species within the body of another species. This approach involves injecting donor pluripotent stem cells into a host blastocyst that lacks critical developmental genes, allowing the donor cells to compensate for the missing organs or tissues in the host and thereby produce organs derived from the donor species. This review consolidates key findings from studies published in the past 2 years, highlighting advancements in techniques that enable the development of functional organs across species, as well as the remaining challenges.

物种间嵌合体已经成为理解组织再生和修复机制的重要工具，为解决全球器官短缺危机提供了有希望的潜力。通过一种被称为种间囊胚互补的技术，研究人员可以在另一个物种的体内培养一个物种的组织和器官。这种方法包括将供体多能干细胞注射到缺乏关键发育基因的宿主囊胚中，使供体细胞补偿宿主体内缺失的器官或组织，从而产生来自供体物种的器官。这篇综述总结了过去两年发表的主要研究成果，强调了跨物种功能器官发育技术的进步，以及仍然存在的挑战。

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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 : 2025-08-01 Epub 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。

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Molecular basis of cell fate plasticity — insights from the privileged cells 细胞命运可塑性的分子基础——来自特权细胞的见解

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-08-01 Epub Date: 2025-05-05 DOI: 10.1016/j.gde.2025.102354

Stephen Maxwell Scalf, Qiao Wu, Shangqin Guo

In the post-Yamanaka era, the rolling balls on Waddington’s hilly landscape not only roll downward, but also go upward or sideways. This new-found mobility implies that the tantalizing somatic cell plasticity fueling regeneration, once only known to planarians and newts, might be sparking in the cells of mice and humans, if only we knew how to fully unlock it. The hope for ultimate regeneration was made even more tangible by the observations that partial reprogramming by the Yamanaka factors reverses many hallmarks of aging [76], even though the underlying mechanism remains unclear. We intend to revisit the milestones in the evolving understanding of cell fate plasticity and glean molecular insights from an unusual somatic cell state, the privileged cell state that reprograms in a manner defying the stochastic model. We synthesize our view of the molecular underpinning of cell fate plasticity, from which we speculate how to harness it for regeneration and rejuvenation. We propose that senescence, aging and malignancy represent distinct cell states with definable biochemical and biophysical parameters.

在后山中时代，沃丁顿丘陵景观上的滚动球不仅向下滚动，而且向上或侧向滚动。这种新发现的移动性意味着，曾经只有涡虫和蝾螈才知道的促进再生的诱人体细胞可塑性，如果我们知道如何完全解开它，可能会在老鼠和人类的细胞中激发出来。Yamanaka因子的部分重编程逆转了衰老的许多特征[76]，尽管其潜在机制尚不清楚，但最终再生的希望变得更加切实。我们打算重新审视对细胞命运可塑性不断发展的理解中的里程碑，并从一种不寻常的体细胞状态中收集分子见解，这种特殊的细胞状态以一种藐视随机模型的方式重新编程。我们综合了我们对细胞命运可塑性的分子基础的看法，从中我们推测如何利用它进行再生和恢复。我们认为衰老、衰老和恶性肿瘤代表不同的细胞状态，具有可定义的生化和生物物理参数。

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引用次数: 0

Rewiring for movements in meiotic prophase: regulators, roles, and evolutionary pathways 减数分裂前期运动的重新布线：调节因子，角色和进化途径

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-08-01 Epub Date: 2025-06-07 DOI: 10.1016/j.gde.2025.102366

Wenxin Xie , Manjunath Gowder , Dominic Bazzano , Morgan DeSantis , Saher S Hammoud

Meiotic prophase movement and chromosome bouquet formation are highly conserved processes and essential features of meiosis, yet their functional components and dependencies vary among organisms. A key feature of meiotic prophase is that chromosome regions like telomeres or centromeres become physically tethered to the inner nuclear membrane through a hierarchical and sequential arrangement of proteins. Telomeres or their analogs further interact with the cytoskeletal machinery, which provides the necessary mechanical force to execute the chromosomal movements that enable homologous pairing, synapsis, and meiotic recombination. Despite decades of research, our understanding of these processes, their interdependencies, and their precise role remains incomplete. Here, we summarize the current mechanistic understanding and describe avenues for further exploration.

减数分裂前期运动和染色体束形成是减数分裂高度保守的过程，是减数分裂的基本特征，但它们的功能成分和依赖关系在不同生物中有所不同。减数分裂前期的一个关键特征是染色体区域，如端粒或着丝粒，通过蛋白质的分层和顺序排列，在物理上与核膜相连。端粒或它们的类似物进一步与细胞骨架机制相互作用，提供必要的机械力来执行染色体运动，使同源配对、突触和减数分裂重组成为可能。尽管经过了几十年的研究，我们对这些过程、它们的相互依赖性以及它们的确切作用的理解仍然不完整。在这里，我们总结了目前的机制理解，并描述了进一步探索的途径。

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 : 2025-08-01 Epub 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

Conservation and divergence of the molecular regulators of the vertebrate fertilization synapse 脊椎动物受精突触分子调控因子的保存与分化

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-08-01 Epub Date: 2025-05-06 DOI: 10.1016/j.gde.2025.102352

Andreas Blaha , Alexander Schleiffer , Andrea Pauli

Fertilization — the process during which sperm and egg find each other, bind and eventually fuse — marks the beginning of a new individual. Research over the past years in vertebrates has shed new light on conserved and divergent molecular regulators that mediate the formation of the fertilization synapse, the close apposition of the two plasma membranes before fusion. Here, we review the known proteins that are required for sperm–egg interaction in mammals and fish from a phylogenetic perspective. While some sperm factors are only conserved in vertebrates and share phylogenetic and structural features, others have a longer evolutionary history. In contrast, the egg factors have changed even within vertebrates despite recognizing the preserved sperm machinery. Future functional work on these factors will be essential to understand the fusion mechanism of vertebrate sperm and egg.

受精——精子和卵子找到彼此，结合并最终融合的过程——标志着一个新个体的开始。在过去的几年里，对脊椎动物的研究揭示了介导受精突触形成的保守和分化的分子调控因子，受精突触是两个质膜在融合前的紧密结合。在这里，我们从系统发育的角度回顾了哺乳动物和鱼类中精子-卵子相互作用所需的已知蛋白质。虽然一些精子因子仅在脊椎动物中保守，并且具有共同的系统发育和结构特征，但其他精子因子具有更长的进化历史。相比之下，即使在脊椎动物中，卵子因子也发生了变化，尽管我们认识到保存精子的机制。今后对这些因子的功能研究将对了解脊椎动物精子和卵子的融合机制至关重要。

引用次数: 0

Stem cell models of human embryo implantation and trophoblast invasion 人胚胎着床和滋养细胞侵袭的干细胞模型

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-08-01 Epub Date: 2025-05-20 DOI: 10.1016/j.gde.2025.102357

Peiheng Liu , Serene Mattis , Thorold W Theunissen

Stem cell–based embryo models have taken the scientific community by storm as they enable investigation of previously inaccessible stages of human development. Here, we discuss how stem cell–based embryo and placenta models can shine a light on two elusive and intertwined aspects of human development that are critical for successful pregnancy: the implantation of the blastocyst into the endometrium and the subsequent invasion of placental villi deep inside the maternal tissues. Both of these processes are mediated by the trophoblast lineage, which is specified in the preimplantation embryo and can be modeled using naïve pluripotent stem cells. We review how embryo and placenta models built from naïve stem cells can be leveraged to obtain mechanistic insights into human implantation and trophoblast invasion.

基于干细胞的胚胎模型已经在科学界掀起了一股风暴，因为它们可以研究以前无法进入的人类发育阶段。在这里，我们讨论了基于干细胞的胚胎和胎盘模型如何揭示人类发育的两个难以捉摸且相互交织的方面，这两个方面对成功怀孕至关重要：囊胚植入子宫内膜和随后胎盘绒毛侵入母体组织深处。这两个过程都是由滋养细胞谱系介导的，滋养细胞谱系是着床前胚胎中指定的，可以使用naïve多能干细胞进行建模。我们回顾了如何利用naïve干细胞构建的胚胎和胎盘模型来获得人类植入和滋养细胞侵袭的机制见解。

引用次数: 0

Rewinding the clock: mechanisms of dedifferentiation 时钟倒转：去分化机制

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Current Opinion in Genetics & Development

Pub Date : 2025-08-01 Epub Date: 2025-04-30 DOI: 10.1016/j.gde.2025.102353

Amelie A Raz , Yukiko M Yamashita

Adult stem cells maintain tissue homeostasis through the production of differentiating cells. Considerable recent work has identified that stem cells themselves are replaceable through the process of dedifferentiation. The capacity and mechanisms of dedifferentiation vary widely among species and organ contexts. However, some core features are commonly present. In this review, we summarize ‘hallmarks’ of dedifferentiation, including mechanisms for maintenance of potency, sensation of loss, and migration, and review the current understanding of dedifferentiation as a true replacement mechanism.

成体干细胞通过产生分化细胞维持组织稳态。最近的大量研究表明，干细胞本身是可以通过去分化过程被替代的。去分化的能力和机制在不同的物种和器官环境中差异很大。然而，一些核心特性通常是存在的。在这篇综述中，我们总结了去分化的“特征”，包括维持效力、丧失感觉和迁移的机制，并回顾了目前对去分化作为一种真正的替代机制的理解。

引用次数: 0

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