Current Opinion in Cell Biology最新文献

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Topological epigenetics: The biophysics of DNA supercoiling and its relation to transcription and genome instability 拓扑表观遗传学：DNA超卷曲的生物物理学及其与转录和基因组不稳定性的关系。

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2025-02-01 DOI: 10.1016/j.ceb.2024.102448

Nick Gilbert , Davide Marenduzzo

Whilst DNA encodes our genetic blueprint as individual nucleobases, as well as epigenetic annotations in the form of biochemical marks, it also carries an extra layer of topological information –, the local over or underwinding of the double helix, known as DNA supercoiling. Supercoiling is a fundamental property of DNA that can be viewed as “topological epigenetics”: it stores energy and structural information, and is tightly linked to fundamental processes; however, its quantification and study, by experiments and modelling alike, is challenging. We review experimental and simulation techniques to study supercoiling and its partition into twist and writhe, especially in the context of chromatin. We then discuss the dynamics of transcription-driven supercoiling in vitro and in vivo, and of supercoiling propagation along mammalian genomes. We finally provide evidence from the literature and potential mechanisms linking this ethereal topological mark to gene expression and chromosome instabilities in genetic diseases and cancer.

DNA 以单个核碱基的形式编码我们的遗传蓝图，并以生化标记的形式进行表观遗传注释，它还携带着一层额外的拓扑信息--双螺旋的局部上卷或下卷，即 DNA 超螺旋。超螺旋是 DNA 的一个基本特性，可被视为 "拓扑表观遗传学"：它存储能量和结构信息，并与基本过程紧密相连；然而，通过实验和建模对其进行量化和研究却极具挑战性。我们回顾了研究超卷曲及其分为扭曲和缠绕的实验和模拟技术，尤其是在染色质的背景下。然后，我们讨论了体外和体内转录驱动的超卷曲动态，以及超卷曲沿哺乳动物基因组传播的动态。最后，我们将提供文献证据和潜在机制，证明这种虚无缥缈的拓扑标记与遗传疾病和癌症中的基因表达和染色体不稳定性有关。

引用次数: 0

Lessons on the force-form-function connection in cell biology from modeling a syncytial germline 从合胞种系建模中汲取细胞生物学中力-形式-功能联系的教训。

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2025-01-31 DOI: 10.1016/j.ceb.2025.102465

John B. Linehan , Michael E. Werner , Amy Shaub Maddox

Germline architecture plays a critical role in the production of functional gametes. Across species, oogenesis involves not only the preparation of the genome for sexual reproduction, but also the dramatic enlargement of a cell compartment to reach a volume sufficient to support embryogenesis. Creating exceptionally large cells is accomplished by a syncytial structure, in which many nucleus-containing compartments are interconnected by cytoplasmic bridges. Maintenance and function of the intricate multi-compartment architecture of syncytia requires cortical contractility, cytoplasmic flows, and germline extrinsic forces that deform and displace the germline and its constituent compartments. The dynamic interplay between local and global force production in shaping syncytial architecture makes the germline an excellent model to study the force-form-function connection in cell biology. Here, we highlight work that has combined physical modeling with cell biological measurements to define the force-form-function connection, using the Caenorhabditis elegans oogenic germline as an archetype.

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引用次数: 0

Sister chromatid cohesion through the lens of biochemical experiments

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2025-01-28 DOI: 10.1016/j.ceb.2025.102464

Yasuto Murayama

Faithful chromosome segregation in eukaryotes relies on physical cohesion between newly duplicated sister chromatids. Cohesin is a ring-shaped ATPase assembly that mediates sister chromatid cohesion through its ability to topologically entrap DNA. Cohesin, assisted by several regulatory proteins, binds to DNA prior to DNA replication and then holds two sister DNAs together when it encounters the replication machinery. Cohesion establishment further requires cohesin acetylation, which confers near eternal stability on chromatin-bound cohesin until the onset of chromosome segregation. In addition to a wealth of experimental evidence from cellular studies, recent advances in reconstitution approaches are now beginning to unravel the biochemical properties of cohesin that underlie its function in sister chromatid cohesion. This review summarizes recent insights into the mechanism of cohesion establishment.

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Autophagic flux measurement: Cargo degradation versus generation of degradation products

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2025-01-27 DOI: 10.1016/j.ceb.2025.102463

Noboru Mizushima

Autophagy is the cellular processes that transport cytoplasmic components to lysosomes for degradation. It plays essential physiological roles, including in adaptation to environmental changes such as starvation and maintaining intracellular quality control. Recently, its links to aging and disease have garnered substantial attention. Although various methods to measure autophagic activity (autophagic flux) have been developed, accurate measurement remains challenging and often contentious. This review presents a discussion of techniques to measure the flux of autophagy, particularly macroautophagy, utilizing two contrasting approaches—assaying cargo degradation versus assaying the generation of degradation products—with an emphasis on the advantages of the latter.

引用次数: 0

Outside Back Cover

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2024-12-01 DOI: 10.1016/S0955-0674(24)00135-2

引用次数: 0

Unleashing XIST from X-chromosome inactivation 从 X 染色体失活中释放 XIST

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2024-11-27 DOI: 10.1016/j.ceb.2024.102446

Céline Morey, Claire Rougeulle, Jean-François Ouimette

Recognition that the most abundant class of genes present in the human genome are those producing long noncoding RNA (lncRNA) has hyped research on this category of transcripts. One such prototypical RNA, Xist, has particularly fueled interest. Initially characterized for its specific expression from the inactive X (Xi), recent studies have uncovered the molecular mechanisms underlying its essential role in the initiation of X-chromosome inactivation, from its exquisitely precise transcriptional regulation to the plethora of protein interactors forming the Xist ribonucleoprotein (RNP) that mediate its gene silencing activity. Here, we will discuss the recent advances that have broadened our knowledge of Xist functions, challenging classical models and revealing unsuspected, unconventional actions of its RNP.

人类基因组中最丰富的一类基因是产生长非编码 RNA（lncRNA）的基因，这一认识催生了对这类转录本的研究。其中一种典型的 RNA--Xist--尤其引起了人们的兴趣。最近的研究揭示了它在启动 X 染色体失活过程中发挥重要作用的分子机制，从其极其精确的转录调控到形成 Xist 核糖核蛋白（RNP）的大量蛋白相互作用者，这些都是其基因沉默活性的介导因素。在这里，我们将讨论最近的研究进展，这些进展拓宽了我们对 Xist 功能的认识，挑战了经典模型，并揭示了其 RNP 未曾预料到的非常规作用。

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Interplay between Notch signaling and mechanical forces during developmental patterning processes 发育模式过程中 Notch 信号与机械力之间的相互作用

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2024-11-27 DOI: 10.1016/j.ceb.2024.102444

Shahar Kasirer , David Sprinzak

The coordination between biochemical signals and cell mechanics has emerged in recent years as a crucial mechanism driving developmental patterning processes across a variety of developing and homeostatic systems. An important class of such developmental processes relies on local communication between neighboring cells through Notch signaling. Here, we review how the coordination between Notch-mediated differentiation and cell mechanics can give rise to unique cellular patterns. We discuss how global and local mechanical cues can affect, and be affected by, cellular differentiation and reorganization controlled by Notch signaling. We compare recent studies of such developmental processes, including the mammalian inner ear, Drosophila ommatidia, intestinal organoids, and zebrafish myocardium, to draw shared general concepts and their broader implications in biology.

近年来，生化信号和细胞机械之间的协调已成为驱动各种发育和平衡系统中发育模式化过程的重要机制。这类发育过程中的一个重要类别依赖于相邻细胞之间通过 Notch 信号进行的局部交流。在此，我们回顾了 Notch 介导的分化与细胞力学之间的协调如何产生独特的细胞模式。我们讨论了全局和局部机械线索如何影响并被 Notch 信号控制的细胞分化和重组所影响。我们比较了对此类发育过程的最新研究，包括哺乳动物内耳、果蝇膜、肠器官和斑马鱼心肌，从而得出共同的一般概念及其在生物学中的广泛意义。

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Design principles of regulatory networks underlying epithelial mesenchymal plasticity in cancer cells 癌细胞上皮间充质可塑性基础调控网络的设计原则

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2024-11-27 DOI: 10.1016/j.ceb.2024.102445

Sarthak Sahoo, Kishore Hari , Mohit Kumar Jolly

Phenotypic plasticity is a hallmark of cancer and drives metastatic disease and drug resistance. The dynamics of epithelial mesenchymal plasticity is driven by complex interactions involving multiple feedback loops in underlying networks operating at multiple regulatory levels such as transcriptional and epigenetic. The past decade has witnessed a surge in systems level analysis of structural and dynamical traits of these networks. Here, we highlight the key insights elucidated from such efforts—a) multistability in gene regulatory networks and the co-existence of many hybrid phenotypes, thus enabling a landscape with multiple ‘attractors’, b) mutually antagonistic ‘teams’ of genes in these networks, shaping the rates of cell state transition in this landscape, and c) chromatin level changes that can alter the landscape, thus controlling reversibility of cell state transitions, allowing cellular memory in the context of epithelial mesenchymal plasticity in cancer cells. Such approaches, in close integration with high-throughput longitudinal data, have improved our understanding of the dynamics of cell state transitions implicated in tumor cell plasticity.

表型可塑性是癌症的标志之一，是转移性疾病和耐药性的驱动因素。上皮间充质可塑性的动态是由在转录和表观遗传等多个调控水平上运行的底层网络中涉及多个反馈回路的复杂相互作用驱动的。过去十年间，对这些网络的结构和动态特征进行系统级分析的热潮席卷全球。在此，我们将重点介绍从这些研究中阐明的关键见解--a）基因调控网络的多稳定性和多种混合表型的共存，从而形成了具有多个 "吸引子 "的景观；b）这些网络中相互拮抗的基因 "团队"，塑造了这一景观中的细胞状态转换率；c）染色质水平的变化可以改变景观，从而控制细胞状态转换的可逆性，使癌细胞上皮间质可塑性背景下的细胞记忆成为可能。这些方法与高通量纵向数据紧密结合，提高了我们对肿瘤细胞可塑性中细胞状态转换动态的理解。

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引用次数: 0

SMC-mediated chromosome organization: Does loop extrusion explain it all? SMC 介导的染色体组织：环状挤压能解释这一切吗？

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2024-11-26 DOI: 10.1016/j.ceb.2024.102447

Tatsuya Hirano, Kazuhisa Kinoshita

In recent years, loop extrusion has attracted much attention as a general mechanism of chromosome organization mediated by structural maintenance of chromosomes (SMC) protein complexes, such as condensin and cohesin. Despite accumulating evidence in support of this mechanism, it is not fully established whether or how loop extrusion operates under physiological conditions, or whether any alternative or additional SMC-mediated mechanisms operate in the cell. In this review, we summarize non-loop extrusion mechanisms proposed in the literature and clarify unresolved issues to further enrich our understanding of how SMC protein complexes work.

近年来，作为由染色体结构维持蛋白（SMC）复合物（如凝聚素和粘合素）介导的染色体组织的一般机制，环挤压引起了广泛关注。尽管有越来越多的证据支持这一机制，但目前尚未完全确定环挤压是否或如何在生理条件下运行，也未确定细胞中是否有任何替代或额外的 SMC 介导的机制。在这篇综述中，我们总结了文献中提出的非环路挤压机制，并澄清了尚未解决的问题，以进一步丰富我们对 SMC 蛋白复合物如何工作的理解。

引用次数: 0

Mechanochemical control systems regulating animal cell size 调节动物细胞大小的机械化学控制系统

IF 6 2区生物学 Q1 CELL BIOLOGY

Current Opinion in Cell Biology

Pub Date : 2024-11-06 DOI: 10.1016/j.ceb.2024.102443

Heather E. Rizzo , Andy L. Zhang , Margaret L. Gardel

Cell size regulation arises from physical manifestations of cell proliferation and metabolic pathways. On one hand, coordination between these systems yields a constant cell size over generations to maintain cell size homeostasis. However, active regulation of cell size is crucial to physiology and to establish broad variation of cell sizes within an individual organism, and is accomplished via physical and biochemical pathways modulated by myriad intrinsic and extrinsic cues. In this review, we explore recent data elucidating the mechanobiological regulation of the volume of animal cells and its coordination with metabolic and proliferative pathways.

细胞大小的调节来自细胞增殖和新陈代谢途径的物理表现。一方面，这些系统之间的协调产生了世代相传的恒定细胞大小，以维持细胞大小的平衡。然而，细胞大小的主动调控对生理学和在单个生物体内建立细胞大小的广泛差异至关重要，并通过由无数内在和外在线索调控的物理和生化途径来实现。在这篇综述中，我们将探讨阐明动物细胞体积的机械生物学调控及其与新陈代谢和增殖途径的协调的最新数据。

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