Nature Reviews Genetics最新文献

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How classical genetics uncovered key determinants of TE silencing. 经典遗传学如何揭示TE沉默的关键决定因素。

IF 52 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-03-25 DOI: 10.1038/s41576-026-00951-5

Emilie Brasset

引用次数: 0

Genetic influences on haematopoiesis. 遗传对造血的影响。

IF 52 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-03-23 DOI: 10.1038/s41576-026-00947-1

Michael Poeschla, Vijay G Sankaran

Haematopoiesis has long been a paradigm for understanding how human genetic variation can influence physiology in health and disease, ranging from the genetic characterization of Mendelian blood diseases to population-scale genomic studies of blood cell phenotypes and diseases. More recently, advances in single-cell genomics and variant-to-function mapping are enabling mechanistic insights into how genetic variation shapes blood cell development. Alongside inherited variation, the characterization of somatic mutations accumulating in haematopoietic stem cells during the lifespan has revealed clonal haematopoiesis as a ubiquitous evolutionary process, with heterogeneous clonal expansions impacting haematopoietic function and disease risk. Insights from genetic studies of haematopoiesis are translating into therapeutic applications, transforming treatment for monogenic blood disorders and promising broader applications. As methods continue to advance, haematopoiesis will remain central to understanding how genetic variation influences human biology, disease susceptibility and therapeutic response.

长期以来，造血一直是理解人类遗传变异如何影响健康和疾病生理学的一个范例，从孟德尔血液病的遗传特征到血细胞表型和疾病的群体规模基因组研究。最近，单细胞基因组学和变异-功能图谱的进展使人们能够深入了解遗传变异如何影响血细胞发育。除了遗传变异外，造血干细胞在生命周期中积累的体细胞突变的特征表明，克隆造血是一个普遍存在的进化过程，异质克隆扩增影响造血功能和疾病风险。来自造血基因研究的见解正在转化为治疗应用，改变单基因血液疾病的治疗方法，并有更广泛的应用前景。随着方法的不断进步，造血仍将是理解遗传变异如何影响人类生物学、疾病易感性和治疗反应的核心。

引用次数: 0

Author Correction: Forensic genetics in the omics era. 作者更正：组学时代的法医遗传学。

IF 42.7 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-03-20 DOI: 10.1038/s41576-026-00953-3

Manfred Kayser

引用次数: 0

Recoding genomes with programmed ribosomal frameshifting. 用程序核糖体移框重新编码基因组。

IF 42.7 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-03-13 DOI: 10.1038/s41576-026-00950-6

Yousuf A Khan

引用次数: 0

Next-generation programmable cell therapies for precision medicine. 用于精准医疗的下一代可编程细胞疗法。

IF 42.7 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-03-11 DOI: 10.1038/s41576-026-00945-3

Ana Palma Teixeira,Dominique Aubel,Martin Fussenegger

Engineered cell therapies are transforming precision medicine by enabling real-time, context-responsive interventions that act upon disease-specific cues. Inspired by the success of CAR-T cells in oncology, next-generation platforms are being developed using diverse immune cells and stem cells to address a broader spectrum of diseases. These living therapeutics harness synthetic gene circuits to induce targeted cytotoxicity, to modulate the secretion of effector proteins or to coordinate both functions in response to endogenous signals or externally delivered molecular and physical triggers. Ex vivo engineering of autologous cells remains the norm, but challenges in scalability, cost and accessibility are fuelling efforts towards allogeneic products and in vivo reprogramming. Advances in targeted delivery - using viral vectors, mRNA-loaded nanoparticles and virus-like particles - are expanding the toolkit for direct programming of cells within the body. This Review discusses emerging strategies for engineering human cells with therapeutic functions, highlighting modular control systems, delivery innovations and the translational hurdles that lie ahead.

工程细胞疗法正在改变精准医疗，它使实时的、对环境有反应的干预措施能够根据疾病的特定线索发挥作用。受CAR-T细胞在肿瘤学领域成功的启发，下一代平台正在开发中，使用多种免疫细胞和干细胞来治疗更广泛的疾病。这些活疗法利用合成基因回路诱导靶向细胞毒性，调节效应蛋白的分泌，或协调这两种功能，以响应内源性信号或外部传递的分子和物理触发。自体细胞的体外工程仍然是常态，但在可扩展性、成本和可及性方面的挑战正在推动异体产品和体内重编程的努力。靶向递送技术的进步——利用病毒载体、装载mrna的纳米颗粒和病毒样颗粒——正在扩大对体内细胞进行直接编程的工具。本综述讨论了具有治疗功能的人类细胞工程的新兴策略，重点介绍了模块化控制系统、交付创新和未来的转化障碍。

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引用次数: 0

Gene regulatory networks: from correlative models to causal explanations. 基因调控网络：从相关模型到因果解释。

IF 42.7 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-03-09 DOI: 10.1038/s41576-026-00939-1

Rory J Maizels,James Briscoe

Gene regulatory networks (GRNs) explain how the genome controls cellular behaviour and tissue morphogenesis, serving to connect molecular mechanism to functional output. Single-cell technologies now provide descriptions of these networks with unprecedented detail, but this advance has also revealed gene regulatory systems that are too complex for our existing conceptual frameworks. GRNs, which should provide mechanistic explanations, are increasingly reduced to statistical correlations - 'hairballs' that fail to capture molecular causation. Here, we explore why this dilemma exists and propose a path forward. We argue that methods in 'representation learning' can be used to model GRNs, without needing to capture every molecular detail. For this framework, we advocate three linked principles: models must be inherently mechanistic, with structures grounded in cellular and evolutionary biology; molecular principles and constraints must be used to reduce the solution space for learning GRN models; and more sophisticated forms of experimental perturbation and synthetic biological engineering are needed to train models and test predictions. By reimagining GRNs through these principles, we can bridge the gap from data abundance to new conceptual understanding.

基因调控网络（grn）解释了基因组如何控制细胞行为和组织形态发生，将分子机制与功能输出联系起来。单细胞技术现在为这些网络提供了前所未有的细节描述，但这一进步也揭示了基因调控系统对于我们现有的概念框架来说过于复杂。grn本应提供机械解释，但却日益沦为统计相关性——无法捕捉分子因果关系的“毛球”。在这里，我们探讨了这种困境存在的原因，并提出了前进的道路。我们认为，“表征学习”中的方法可以用于对grn建模，而无需捕获每个分子细节。对于这个框架，我们主张三个相互联系的原则：模型必须具有内在的机械性，其结构以细胞和进化生物学为基础；必须使用分子原理和约束来减小学习GRN模型的解空间；需要更复杂形式的实验扰动和合成生物工程来训练模型和测试预测。通过这些原则重新构想grn，我们可以弥合从数据丰富到新概念理解的差距。

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引用次数: 0

Epistasis and co-adaptation in bacterial genome evolution. 细菌基因组进化中的上位性和共适应。

IF 42.7 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-03-02 DOI: 10.1038/s41576-026-00941-7

Elizabeth A Cummins,Priyanshu Singh Raikwar,Eve Hallett,Samuel K Sheppard

Precise genotype-phenotype mapping is essential in applied microbiology, from engineering genetically modified strains to developing tailored strategies for antimicrobial therapies. Comparative genomics often treats genes as independent contributors to phenotypes, and gene knockout and complementation remain the gold standard to validate genotype-phenotype associations in microorganisms. However, genes do not act in isolation, and complex gene-gene interactions, that is, epistatic interactions, are essential for the evolution and function of bacterial genomes. Recent advances in high-throughput genomics and experimental techniques have enabled systematic screens of epistasis in bacteria at scale, revealing mechanisms underlying epistasis and co-adaptation in laboratory and wild populations. Here we review how microbial genomics is moving beyond gene-centric models towards integrated analyses of potentiating, compensatory and context-dependent variation. The timely incorporation of interaction-based perspectives into population-scale analyses will improve genotype-phenotype mapping and the understanding of the complex traits that shape the microbial world.

精确的基因型-表型定位在应用微生物学中是必不可少的，从工程转基因菌株到开发量身定制的抗菌治疗策略。比较基因组学通常将基因视为表型的独立贡献者，基因敲除和基因互补仍然是验证微生物基因型-表型关联的金标准。然而，基因并不是孤立地起作用的，复杂的基因-基因相互作用，即上位相互作用，对细菌基因组的进化和功能至关重要。高通量基因组学和实验技术的最新进展使大规模细菌上位性的系统筛选成为可能，揭示了实验室和野生种群中上位性和共同适应的机制。在这里，我们回顾了微生物基因组学如何超越以基因为中心的模型，走向增强、补偿和环境依赖变异的综合分析。及时将基于相互作用的观点纳入种群规模分析将改善基因型-表型定位和对塑造微生物世界的复杂性状的理解。

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引用次数: 0

Charting single-cell lineages with synthetic and natural barcodes. 用合成和天然条形码绘制单细胞谱系图。

IF 52 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-02-27 DOI: 10.1038/s41576-026-00943-5

Alejo E Rodriguez-Fraticelli, Victoria Parreno

Across our lifespan, cells divide and differentiate to create the functional units of all organs, yet with age and cancer a small number of cellular families (clones) will rule the fate of the organism. Advances in synthetic and natural barcoding methods now enable cellular ancestries to be reconstructed with unprecedented single-cell resolution. These single-cell lineage-tracing studies are leading to a re-evaluation of long-standing paradigms in development, ageing and cancer biology and are revealing the underpinnings of phenotypic heterogeneity for various cellular functions, including regeneration and stress responses. Despite remaining methodological challenges, progress continues towards multimodal tracing methods that combine spatial, genetic, epigenetic and transcriptomic information. The future transition of clonal analysis into the clinic may eventually help detect, predict and prevent disease progression.

在我们的一生中，细胞分裂和分化创造出所有器官的功能单位，然而随着年龄和癌症的增长，少数细胞家族（克隆）将统治生物体的命运。合成和自然条形码方法的进步现在使细胞祖先能够以前所未有的单细胞分辨率重建。这些单细胞谱系追踪研究导致了对发育、衰老和癌症生物学中长期存在的范式的重新评估，并揭示了各种细胞功能（包括再生和应激反应）的表型异质性基础。尽管方法学上仍存在挑战，但结合空间、遗传、表观遗传和转录组信息的多模式追踪方法仍在取得进展。克隆分析的未来过渡到临床可能最终有助于检测，预测和预防疾病进展。

引用次数: 0

From DNA microarrays to somatic mosaicism in population cohorts 从DNA微阵列到群体群体中的体细胞嵌合体

IF 42.7 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-02-24 DOI: 10.1038/s41576-026-00948-0

Chikashi Terao

引用次数: 0

A codon-resolved view of subcellular translation with LOCL-TL 用LOCL-TL分析亚细胞翻译的密码子解析观点

IF 42.7 1区生物学 Q1 GENETICS & HEREDITY

Nature Reviews Genetics

Pub Date : 2026-02-17 DOI: 10.1038/s41576-026-00946-2

Jingchuan Luo

引用次数: 0

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