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Cancer-associated fibroblasts as mediators of tissue microenvironment remodeling in cancer 癌症相关成纤维细胞作为癌症组织微环境重塑的介质
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-07-14 DOI: 10.1016/j.ceb.2025.102567
Fernanda G. Kugeratski , Emily J. Kay , Sara Zanivan
Cancer-associated fibroblasts (CAFs) are a multifunctional cell population of solid tumors that substantially remodel the tumor microenvironment (TME). The combination of single-cell and spatial technologies with elegant mouse models and analysis of patient samples is enabling unprecedented advances in the characterization of CAF origins, heterogeneity, and functions within the TME. As such, the field is now evolving to delineate tissue-specific subpopulations of CAFs, their markers, and the biological context in which each subset presents with a tumor-promoting or a tumor-restraining function. In this timely review, we discuss recent advances in CAF biology in the context of emerging areas of interest in the field of anticancer therapy: immunotherapy, metabolism, and extracellular vesicles. We also highlight the substantial role of CAFs in modulating the immune microenvironment and the recent advances in targeting CAFs for cancer treatment.
癌症相关成纤维细胞（CAFs）是一种多功能的实体肿瘤细胞群，可以重塑肿瘤微环境（TME）。将单细胞和空间技术与优雅的小鼠模型和患者样本分析相结合，使得在TME内CAF起源、异质性和功能的表征方面取得了前所未有的进展。因此，该领域现在正在发展，以描述caf的组织特异性亚群，其标记物以及每个亚群具有肿瘤促进或肿瘤抑制功能的生物学背景。在这篇及时的综述中，我们讨论了CAF生物学在抗癌治疗领域新兴领域的最新进展：免疫治疗、代谢和细胞外囊泡。我们还强调了CAFs在调节免疫微环境中的重要作用，以及针对CAFs进行癌症治疗的最新进展。
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引用次数: 0
Mathematical modelling of cancer cell evolution and plasticity 癌细胞进化和可塑性的数学建模
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-07-09 DOI: 10.1016/j.ceb.2025.102558
Chloé Colson, Frederick JH. Whiting, Ann-Marie Baker, Trevor A. Graham
In this review, we argue that mathematical modelling is an essential tool for understanding cancer cell evolution and phenotypic plasticity. We show that mathematical models enable us to reconstruct time-dependent tumour evolutionary dynamics from temporally-restricted biological data. In their ability to capture complex biological processes, they also serve as a means for in silico experimentation. In particular, they allow us to investigate different biological hypotheses and generate experimentally-testable predictions about underlying mechanisms of phenotype evolution and treatment resistance. Finally, mathematical models can reveal which biological data is informative, and, in combination with our understanding of which biological hypotheses need to be tested, they can guide experimental and clinical trial design.
在这篇综述中，我们认为数学建模是理解癌细胞进化和表型可塑性的重要工具。我们表明，数学模型使我们能够重建时间依赖的肿瘤进化动力学从时间限制的生物数据。在捕捉复杂生物过程的能力上，它们也可以作为计算机实验的一种手段。特别是，它们使我们能够研究不同的生物学假设，并产生关于表型进化和治疗抗性的潜在机制的实验可测试的预测。最后，数学模型可以揭示哪些生物学数据是有用的，并且，结合我们对哪些生物学假设需要测试的理解，它们可以指导实验和临床试验设计。
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引用次数: 0
Signaling mechanisms in the reactivation of quiescent neural stem cells in Drosophila 果蝇静止神经干细胞再激活的信号机制
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-07-07 DOI: 10.1016/j.ceb.2025.102566
Mahekta R. Gujar , Hongyan Wang
Neural stem cells (NSCs) play a central role in the nervous system development and regeneration. In the adult mammalian brain, most NSCs remain in a quiescent state, but they can exit quiescence and become active, leading to the generation of new neurons. Maintaining a balance between NSC quiescence and activation is important for adult neurogenesis. Similar to their mammalian counterparts, Drosophila NSCs transition between quiescence and reactivation. This review summarizes the latest insights into the molecular processes driving the reactivation of quiescent NSCs in the Drosophila larval brain. We focus on recent advances in stem cell niches, cytoskeletal proteins, and both transcriptional and posttranslational regulations during NSC reactivation, as well as a new regeneration model in the Drosophila brain.
神经干细胞（NSCs）在神经系统发育和再生中起着核心作用。在成年哺乳动物大脑中，大多数NSCs保持静止状态，但它们可以退出静止状态并变得活跃，从而产生新的神经元。维持NSC静止和激活之间的平衡对成人神经发生很重要。与哺乳动物类似，果蝇的NSCs在静止和再激活之间转换。本文综述了在果蝇幼虫大脑中驱动静止NSCs再激活的分子过程的最新见解。我们关注干细胞龛，细胞骨架蛋白，NSC再激活过程中的转录和翻译后调控的最新进展，以及果蝇大脑中的新再生模型。
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引用次数: 0
Arp2/3-complex regulation – Novel insights and open questions arp2 /3-复杂的规则-新颖的见解和开放的问题
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-06-25 DOI: 10.1016/j.ceb.2025.102565
Theresia E.B. Stradal , Micaela Boiero Sanders , Peter Bieling
Arp2/3 complex is a central actin filament generator driving numerous motile processes in cells. It was originally isolated from Acanthamoeba approx. 30 years ago. It is highly conserved throughout eukaryotic life and composed of 7 subunits, two of which are actin related proteins, ARP2 and ARP3. Since then the modalities of its regulation were continuously unraveled, bringing about a large number of proteins that affect its activity. We here set out to briefly review our current knowledge and identify open questions that demand answers and add new twists, advancing our understanding to reflect physiological complexity.
Arp2/3复合体是驱动细胞中许多运动过程的中心肌动蛋白丝发生器。它最初是从棘阿米巴原虫中分离出来的。30年前。它在整个真核生命中高度保守，由7个亚基组成，其中两个是肌动蛋白相关蛋白ARP2和ARP3。从那时起，它的调节模式不断被解开，带来了大量影响其活性的蛋白质。在这里，我们将简要回顾我们目前的知识，并确定需要回答的开放性问题，并添加新的曲折，推进我们的理解，以反映生理的复杂性。
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引用次数: 0
Mechanisms of left–right symmetry breaking across scales 跨尺度的左右对称破缺机制
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-06-21 DOI: 10.1016/j.ceb.2025.102564
Nikoloz Tsikolia , Dinh Thach Lam Nguyen , Yee Han Tee
Establishment of left–right (LR) asymmetry relies on a multistep interplay of molecular signaling and physical processes. Initial LR symmetry breaking in several model vertebrates was shown to take place at the LR organizer (LRO) where chiral rotation of monocilia produces a leftward fluid flow. Subsequent bending of sensory cilia triggers Pkd2-channel–mediated calcium transients which in turn are required for induction of asymmetrical signaling upstream of morphological asymmetries, emphasizing the role of mechanosensation in flow detection. Crucially, unidirectional flow and its detection were suggested to require cellular-scale asymmetries including planar cell polarity–mediated posterior position and ultrastructural chirality of motile cilia as well as asymmetric Pkd2 localization within sensory cilia. Alternative mechanisms of LR symmetry breaking operate in models like the chick embryo, where asymmetry of gene expression is preceded by leftward primitive node rotation suggesting mechanisms based on cytoskeletal chirality known from invertebrate models including Caenorhabditis elegans and fruit fly. Investigation of chirality at the cellular level suggests that chirality of components of cytoskeleton, particularly actin filaments, is amplified by distinct modules based i.e. on formin-actin and myosin-actin interactions which drive intracellular swirling and cortical flow, providing a basis for LR asymmetry. Cellular chirality can organize LR asymmetry of multicellular behavior as observed in the chiral alignment of fibroblasts. The integration of molecular, cellular, and tissue-scale chirality highlights conserved and divergent mechanisms underpinning LR symmetry breaking across species. Unraveling these processes may illuminate pathways connecting cytoskeletal dynamics to organismal asymmetry, offering insights into development and evolution.
左右（LR）不对称的建立依赖于分子信号和物理过程的多步骤相互作用。在一些模型脊椎动物中，最初的LR对称性破坏被证明发生在LR组织者（LRO），其中单纤毛的手性旋转产生向左的流体流动。随后感觉纤毛的弯曲触发pkd2通道介导的钙瞬态，这反过来又是诱导形态不对称上游的不对称信号所必需的，强调了机械感觉在血流检测中的作用。重要的是，单向流动及其检测需要细胞尺度的不对称性，包括平面细胞极性介导的后位置和运动纤毛的超微结构手性，以及感觉纤毛内Pkd2的不对称定位。另一种LR对称性破坏机制在鸡胚等模型中起作用，在鸡胚中，基因表达的不对称之前是向左的原始节点旋转，这表明基于细胞骨架手性的机制是从秀丽隐杆线虫和果蝇等无脊椎动物模型中已知的。在细胞水平上对手性的研究表明，细胞骨架成分的手性，特别是肌动蛋白丝的手性，被不同的模块放大，即formmin -actin和my球蛋白-actin相互作用，驱动细胞内旋转和皮质流动，为LR不对称提供了基础。在成纤维细胞的手性排列中观察到，细胞手性可以组织多细胞行为的LR不对称性。分子、细胞和组织尺度手性的整合突出了跨物种LR对称性破缺的保守和分歧机制。解开这些过程可能阐明连接细胞骨架动力学与生物体不对称的途径，为发育和进化提供见解。
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引用次数: 0
Macropinocytosis: Molecular mechanisms and regulation 巨量红细胞增多症：分子机制和调控
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-06-17 DOI: 10.1016/j.ceb.2025.102563
Hui Tu , Haibin Wang , Huaqing Cai
Macropinocytosis is a conserved pathway for non-selective bulk uptake of extracellular fluid. It plays important roles in various cellular processes, including nutrient acquisition in Dictyostelium and cancer cells and antigen sampling by immune cells. This process is initiated by localized actin polymerization, which drives the formation of membrane protrusions that close to generate macropinosomes. Once formed, macropinosomes undergo maturation and traffic through the endolysosomal system for cargo degradation, whereas non-degradable material is exocytosed. Recent studies have uncovered conserved regulatory networks controlling macropinosome formation and maturation. This review provides an overview of these pathways, highlighting key molecular regulators and their coordinated responses to environmental signals. We also examine the interplay between macropinocytosis and cell migration, discussing potential mechanisms that balance these processes to optimize cellular function.
巨量胞饮是一种非选择性大量摄取细胞外液的保守途径。它在各种细胞过程中发挥重要作用，包括盘基骨柱和癌细胞的营养获取以及免疫细胞的抗原取样。这个过程是由局部肌动蛋白聚合引发的，它驱动膜突起的形成，靠近产生巨肽体。一旦形成，大蛋白酶体通过内溶酶体系统进行成熟和运输以降解货物，而不可降解的物质则被胞吐。最近的研究发现了控制大肌醇体形成和成熟的保守调控网络。本文综述了这些途径，重点介绍了关键的分子调节因子及其对环境信号的协调反应。我们还研究了巨量红细胞增多症和细胞迁移之间的相互作用，讨论了平衡这些过程以优化细胞功能的潜在机制。
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引用次数: 0
Nuclear biophysics: Spatial coordination of transcriptional dynamics? 核生物物理学：转录动力学的空间协调？
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-06-14 DOI: 10.1016/j.ceb.2025.102561
Tae Yeon Yoo , Bernardo Gouveia , Daniel Needleman
A great deal is known about biochemical aspects of transcription, but we still lack an understanding of how transcription is causally regulated in space and time. A major unanswered question is the extent to which transcription at different locations in the nucleus are independent from each other or, instead, are spatially coordinated. We propose two classes of models of coordination: 1) the shared environment model, in which neighboring loci exhibit coordinated transcriptional dynamics due to sharing the same local biochemical environment; 2) the mechanical crosstalk model, in which forces propagate from one actively transcribing locus to affect transcription of another. Determining the prevalence of the spatial coordination of transcription, and the underlying mechanisms when it occurs, is an exciting challenge in nuclear biophysics.
我们对转录的生化方面了解很多，但我们仍然缺乏对转录如何在空间和时间上受到因果调节的理解。一个主要的悬而未决的问题是，在多大程度上转录在细胞核的不同位置是相互独立的，或者相反，是空间协调。我们提出了两类协调模型：1)共享环境模型，其中相邻基因座由于共享相同的局部生化环境而表现出协调的转录动力学；2)机械串扰模型，其中力从一个主动转录位点传播到另一个转录位点。确定转录空间协调的普遍性及其发生时的潜在机制，是核生物物理学中令人兴奋的挑战。
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引用次数: 0
Advances in single-cell omics: Transformative applications in basic and clinical research 单细胞组学进展：在基础和临床研究中的变革性应用
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-06-14 DOI: 10.1016/j.ceb.2025.102548
Mohammed Inayatullah , Anuj Kumar Dwivedi , Vijay K. Tiwari
Recent advancements in single-cell RNA sequencing, spatial transcriptomics, and multi-omics integration have enabled researchers to dissect complex tissues and identify distinct cell populations with unique functional states. This review discusses the application of single-cell omics in diverse fields, including cancer research and developmental biology, showcasing how they reveal insights into cellular interactions, disease mechanisms, and therapeutic responses. Notable studies illustrate the potential of single-cell approaches to uncover novel biomarkers and therapeutic targets, particularly in heterogeneous diseases such as cancer and neurodevelopmental disorders. Furthermore, the review emphasizes the importance of integrating single-cell data with computational models to enhance our understanding of cellular dynamics and microenvironmental influences. Overall, this review underscores the critical role of single-cell omics in advancing our knowledge of biology and its applications in clinical settings, paving the way for personalized medicine.
单细胞RNA测序、空间转录组学和多组学整合的最新进展使研究人员能够解剖复杂组织并识别具有独特功能状态的不同细胞群。这篇综述讨论了单细胞组学在不同领域的应用，包括癌症研究和发育生物学，展示了它们如何揭示细胞相互作用、疾病机制和治疗反应。值得注意的研究表明，单细胞方法在发现新的生物标志物和治疗靶点方面具有潜力，特别是在癌症和神经发育障碍等异质性疾病中。此外，该综述强调了将单细胞数据与计算模型相结合的重要性，以增强我们对细胞动力学和微环境影响的理解。总的来说，这篇综述强调了单细胞组学在推进我们的生物学知识及其在临床环境中的应用方面的关键作用，为个性化医疗铺平了道路。
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引用次数: 0
From brain-sparing to prioritised tumour growth: Insights into tumour-host interactions 从脑保留到肿瘤优先生长：对肿瘤-宿主相互作用的见解
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-06-13 DOI: 10.1016/j.ceb.2025.102560
Qian Dong , Louise Y. Cheng
Cellular responses to their environment are shaped not only by genetic composition but also by interactions with neighbouring cells. Beyond local interactions, inter-organ crosstalk has emerged as a crucial mechanism coordinating tissue growth and function. In this review, we discuss recent findings, mainly using Drosophila as a model system to investigate how organs compete for resources under metabolic stress. This mechanism ensures the prioritized growth of essential organs during development and the growth of tumours at the expense of other tissues and host fitness. Together, these studies offered valuable insights into how inter-organ communications via secreted factors and host resource reallocation are important in affecting tissue fitness and driving disease progression.
细胞对环境的反应不仅受基因组成的影响，还受与邻近细胞的相互作用的影响。除了局部相互作用外，器官间的相互作用已成为协调组织生长和功能的重要机制。在这篇综述中，我们讨论了最近的发现，主要是利用果蝇作为模型系统来研究代谢应激下器官如何竞争资源。这种机制确保了在发育过程中重要器官的优先生长和肿瘤的生长，而牺牲了其他组织和宿主的健康。总之，这些研究提供了有价值的见解，通过分泌因子和宿主资源重新分配的器官间通信如何在影响组织健康和驱动疾病进展中发挥重要作用。
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引用次数: 0
Evolution of the cytoskeleton: Emerging clues from the diversification and specialisation of archaeal cytoskeletal proteins 细胞骨架的进化：从古细菌细胞骨架蛋白的多样化和特化中出现的线索
IF 6 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-06-12 DOI: 10.1016/j.ceb.2025.102557
Hannah J. Brown, Vinaya D. Shinde, Leonardo Bosi, Iain G. Duggin
Recent research in archaeal cell biology has revealed a remarkable diversity of cytoskeletal proteins related to those found in bacteria and eukaryotes, such as the tubulin, actin, and ESCRT protein superfamilies, and archaea-specific proteins that self-assemble and have been implicated in cytoskeletal roles. Here, we outline an emerging view that the archaeal cytoskeleton has several conceptual ties to the sophisticated eukaryotic cytoskeleton. We highlight that duplication and specialisation of protein function is common among archaeal cytoskeletal systems, and that some paralogues show coordinated, opposing functions in the regulation of cell morphogenesis and structural homeostasis. Furthermore, the presence of homologues of eukaryotic cytoskeletal regulators in Asgard archaea, the closest known relatives of eukaryotes, underscores further linkages between eukaryotic and increasingly sophisticated archaeal cytoskeletal systems.
最近对古细菌细胞生物学的研究揭示了与细菌和真核生物中发现的细胞骨架蛋白相关的显著多样性，如微管蛋白、肌动蛋白和ESCRT蛋白超家族，以及自组装并参与细胞骨架作用的古细菌特异性蛋白。在这里，我们概述了一种新兴的观点，即古细菌细胞骨架与复杂的真核细胞骨架有几个概念上的联系。我们强调，蛋白质功能的复制和专门化在古细菌细胞骨架系统中是常见的，并且一些类似物在细胞形态发生和结构稳态的调节中显示出协调的，相反的功能。此外，真核生物的近亲阿斯加德古菌中真核细胞骨架调节因子同源物的存在，进一步强调了真核生物和日益复杂的古菌细胞骨架系统之间的联系。
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引用次数: 0
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