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Special issue: “Novel functions of programmed cell death in development: Current status and future challenges” 特刊:“细胞程序性死亡在发育中的新功能:现状和未来挑战”
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-10-01 Epub Date: 2025-07-28 DOI: 10.1016/j.semcdb.2025.103637
Romain Levayer
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引用次数: 0
Force of change: How biomechanical cues drive endothelial plasticity and morphogenesis 变化的力量:生物力学线索如何驱动内皮可塑性和形态发生。
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-07-02 DOI: 10.1016/j.semcdb.2025.103623
Dorothee Bornhorst , Newsha Mortazavi , Felix Gunawan
Endothelial cells (ECs), which line the inner surface of blood vessels, continuously respond to biomechanical forces from blood flow, extracellular matrix, and intracellular tension. Recent advances have highlighted the pivotal role of these forces in regulating cellular plasticity during endothelial-to-hematopoietic transition (EHT) and endothelial-to-mesenchymal transition (EndMT), two processes essential for embryogenesis, tissue repair, and disease progression. EHT contributes to hematopoietic stem cell formation, and EndMT to valve formation and vessel sprouting. When misregulated, both processes cause vascular pathologies such as fibrosis, cancer metastasis, and atherosclerosis. This review provides an overview of how biomechanical cues influence EC fate decisions and behavioral transitions. We explore how external biomechanical forces are sensed at the endothelial cell surface, transmitted through intracellular adaptors, and affect changes at the transcriptional level. Understanding these mechanotransduction pathways during cell fate transition not only deepens our knowledge of endothelial cell plasticity but also provides insight into potential root causes of and treatments for vascular diseases.
内皮细胞(ECs)排列在血管的内表面,不断地对来自血流、细胞外基质和细胞内张力的生物力学力做出反应。最近的进展强调了这些力量在内皮-造血转化(EHT)和内皮-间充质转化(EndMT)过程中调节细胞可塑性的关键作用,这两个过程对胚胎发生、组织修复和疾病进展至关重要。EHT有助于造血干细胞的形成,而EndMT有助于瓣膜的形成和血管的发芽。当调控不当时,这两个过程都会引起血管病变,如纤维化、癌症转移和动脉粥样硬化。这篇综述概述了生物力学线索如何影响EC命运决定和行为转变。我们探索外部生物力学力如何在内皮细胞表面被感知,通过细胞内接头传递,并影响转录水平的变化。了解细胞命运转变过程中的这些机械转导途径不仅加深了我们对内皮细胞可塑性的认识,而且为血管疾病的潜在根本原因和治疗提供了见解。
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引用次数: 0
Establishment & maintenance of collective cell migration in angiogenesis: Lessons from zebrafish 血管生成中集体细胞迁移的建立和维持:来自斑马鱼的经验
IF 6.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-07-15 DOI: 10.1016/j.semcdb.2025.103627
Brendan Capey, Shane P. Herbert
During tissue development, growth and regeneration, assembly of almost all new blood and lymphatic vessels arises via their branching from pre-existing vessels, processes termed angiogenesis and lymphangiogenesis, respectively. Furthermore, imbalances in these branching processes contribute to numerous disease states, including cancer, blindness, arthritis and ischemic disorders. At its core, new vessel branching is driven by the coordinated collective migration of specialized endothelial “tip” cells that lead sprouting vessels and “stalk” cells that trail the tip. Thus, studies defining the fundamental mechanisms directing angiogenesis and lymphangiogenesis not only have key therapeutic implications but have also defined core conserved principles dictating collective cell migration. In this review we focus on recent insights into the roles of intracellular, intercellular and cell morphology-driven positive- and negative-feedback loops in the establishment and maintenance of tip versus stalk cell identities and behaviour. Moreover, we highlight recent insights into the role of asymmetric cell divisions in self-organisation of the tip-stalk cell hierarchy during vessel assembly. Considering that many of the principles underpinning collective movement are broadly conserved between tissue systems, concepts described here likely play key roles in the control of collective cell migration in diverse tissue contexts.
在组织发育、生长和再生过程中,几乎所有的新血液和淋巴管的形成都是通过原有血管的分支形成的,这一过程分别被称为血管生成和淋巴管生成。此外,这些分支过程的不平衡导致许多疾病状态,包括癌症、失明、关节炎和缺血性疾病。在其核心,新的血管分支是由专门的内皮“尖端”细胞的协调集体迁移驱动的,“尖端”细胞引导发芽血管和“茎”细胞跟踪尖端。因此,研究确定了指导血管生成和淋巴管生成的基本机制不仅具有关键的治疗意义,而且还定义了决定集体细胞迁移的核心保守原则。在这篇综述中,我们将重点关注细胞内、细胞间和细胞形态驱动的正反馈和负反馈回路在尖端与柄细胞身份和行为的建立和维持中的作用。此外,我们强调了最近对不对称细胞分裂在导管组装过程中尖端柄细胞层次自组织中的作用的见解。考虑到支持集体运动的许多原则在组织系统之间广泛保守,这里描述的概念可能在不同组织背景下控制集体细胞迁移中发挥关键作用。
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引用次数: 0
Coping with uncertainty: Challenges for robust pattern formation in dynamical tissues 应对不确定性:动态组织中稳健模式形成的挑战
IF 6.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-07-08 DOI: 10.1016/j.semcdb.2025.103629
Tony Yu-Chen Tsai , Diana Pinheiro
An outstanding question in biology is how tissue patterning emerges during development. The concept of positional information, which posits that gradients of morphogens instruct cell fate in a concentration-dependent manner, has been an influential framework to understand pattern formation. Recent studies, however, highlight that developing tissues are highly dynamic, with cellular movements, arising from local mechanical fluctuations or global morphogenetic forces, that often coincide with morphogen signaling and cell fate specification. This calls for a more dynamic understanding of pattern formation by explicitly investigating the interplay between signaling, cell fate and morphogenesis. In this review, we first discuss emerging evidence on the role of cellular movements in modulating signaling dosage and cell fate acquisition. We then examine the biophysical strategies employed by developing tissues to achieve robust patterning despite ongoing cellular dynamics and large-scale morphogenesis. While cellular movements may intuitively be viewed as disruptive to patterning programs, recent evidence suggests that when coupled with cell fate, they can act as a critical mechanism for generating and stabilizing precise tissue patterns during development.
生物学中一个突出的问题是组织模式是如何在发育过程中出现的。位置信息的概念,假设形态因子的梯度以浓度依赖的方式指导细胞命运,已经成为理解模式形成的一个有影响力的框架。然而,最近的研究强调,发育中的组织是高度动态的,细胞运动是由局部机械波动或整体形态发生力量引起的,这往往与形态发生信号和细胞命运规范相吻合。这就要求通过明确地研究信号、细胞命运和形态发生之间的相互作用,对模式形成有更动态的理解。在这篇综述中,我们首先讨论了关于细胞运动在调节信号剂量和细胞命运获取中的作用的新证据。然后,我们研究了发展组织所采用的生物物理策略,尽管正在进行的细胞动力学和大规模形态发生,但仍能实现稳健的模式。虽然细胞运动可能被直观地视为破坏模式程序,但最近的证据表明,当与细胞命运相结合时,它们可以作为在发育过程中产生和稳定精确组织模式的关键机制。
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引用次数: 0
Curvature feedback for repetitive tissue morphogenesis – Bridging algorithmic principles and self-regulatory systems 重复组织形态发生的曲率反馈-桥接算法原理和自我调节系统
IF 6.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-07-04 DOI: 10.1016/j.semcdb.2025.103633
Emmanuel Vikran , Tsuyoshi Hirashima
Tissue patterning during organ development consists of intricate morphogenetic processes, driven by the interplay of physical and genetic cues among constituent cells. Despite its complexity, these processes can be decomposed into fundamental morphogenetic motifs that appear repeatedly in a spatiotemporally organized manner, giving rise to diverse organ architectures. Recent studies have highlighted tissue-scale curvature as critical information for constitutive cells, which enables it to bridge mechanical and biochemical signals. In this review, we discuss the regulatory principles underlying the roles of tissue curvature in morphogenesis along with recent insights from earlier studies. Here, we focus on the dual role of tissue curvature as an instructive signal that directs collective cell behavior and as a dynamic property modulated by cellular activities. First, we introduce the concept of morphogenetic motifs and provide examples from developmental processes in various organ systems. Next, we discuss how cells collectively respond to two distinct curvature types, lateral and topographical, and examine the mechanisms by which cells sense these curvatures from a mechanobiological perspective. Finally, we highlight the repetitive terminal bifurcation in developing murine lung epithelium, illustrating how curvature-driven feedback loops, mediated through mechano-chemical multicellular couplings, ensure robust morphogenetic cycles. By integrating geometric, mechanical, and chemical cues, curvature feedback emerges as a framework for self-organized morphogenesis, providing fresh perspectives on the recurrent properties and robustness of development.
器官发育过程中的组织模式由复杂的形态发生过程组成,由组成细胞之间的物理和遗传信号相互作用驱动。尽管复杂,但这些过程可以分解为基本的形态发生基序,这些基序以时空组织的方式反复出现,从而产生不同的器官结构。最近的研究强调,组织尺度的曲率是构成细胞的关键信息,使其能够连接机械和生化信号。在这篇综述中,我们讨论了组织曲率在形态发生中的作用的调节原理以及早期研究的最新见解。在这里,我们关注组织曲率作为指导集体细胞行为的指向性信号和作为细胞活动调节的动态特性的双重作用。首先,我们介绍了形态发生基序的概念,并从各种器官系统的发育过程中提供了例子。接下来,我们讨论细胞如何集体响应两种不同的曲率类型,横向和地形,并从机械生物学的角度检查细胞感知这些曲率的机制。最后,我们强调了发育中的小鼠肺上皮的重复末端分叉,说明了曲率驱动的反馈回路如何通过机械-化学多细胞偶联介导,确保稳健的形态发生周期。通过整合几何、机械和化学线索,曲率反馈作为自组织形态发生的框架出现,为循环特性和发展的稳健性提供了新的视角。
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引用次数: 0
Collective cell migration across scales: A systems perspective 跨尺度的集体细胞迁移:系统视角
IF 6.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-07-08 DOI: 10.1016/j.semcdb.2025.103628
Zimeng Wu , Mie Wong
Collective cell migration is a key tissue shaping process fundamental to development, wound healing and cancer invasion. The sensing, integration, transduction and propagation of guidance signals and the resulting generation of collective cell responses during collective cell migration can occur at several different length scales from molecular to cellular to supracellular. Furthermore, we have become aware that the cell-environment relationship during migration is bi-directional, where cells not only receive guidance cues from the environment, but also dynamically remodel the environment via their migratory behaviours. Such complex interplay of internal (i.e. intracellular) and external (i.e. cell-cell and cell-environment) interactions makes predicting the emergent output behaviours of cell groups challenging. Here, we propose a framework that combines interdisciplinary experimental and theoretical approaches to bridge the gap between molecular-level mechanisms and tissue-level phenomena during collective cell migration in complex environments. We will review recent works on both in vitro and in vivo migratory models that successfully employ some of these approaches to identify general principles explaining the input-output relationships of robustly tuneable migratory systems. By integrating in vitro with in vivo observations, we will develop more comprehensive models of how collective cell migration is orchestrated in living organisms, which will also pave the way for more effective applications in tissue engineering and disease therapeutics in the future.
集体细胞迁移是一个关键的组织形成过程,对发育、伤口愈合和癌症侵袭至关重要。在集体细胞迁移过程中,引导信号的感知、整合、转导和传播以及由此产生的集体细胞反应可以发生在从分子到细胞再到超细胞的几个不同长度尺度上。此外,我们已经意识到,在迁移过程中,细胞与环境的关系是双向的,细胞不仅接受来自环境的引导线索,而且通过它们的迁移行为动态地重塑环境。这种内部(即细胞内)和外部(即细胞-细胞和细胞-环境)相互作用的复杂相互作用使得预测细胞群的紧急输出行为具有挑战性。在这里,我们提出了一个结合跨学科实验和理论方法的框架,以弥合复杂环境中集体细胞迁移过程中分子水平机制和组织水平现象之间的差距。我们将回顾最近在体外和体内迁移模型上的工作,这些模型成功地采用了其中一些方法来确定解释稳健可调迁移系统的投入-产出关系的一般原则。通过结合体外和体内观察,我们将开发出更全面的模型,研究生物体中集体细胞迁移是如何协调的,这也将为未来在组织工程和疾病治疗中更有效的应用铺平道路。
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引用次数: 0
The open and closed case for Class I HDACs in cardiac development I类hdac在心脏发育中的开放和封闭案例
IF 6.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-01 Epub Date: 2025-06-09 DOI: 10.1016/j.semcdb.2025.103621
Drishti Rajesth, Veronica Uribe , Kelly A. Smith
Gene expression in cardiac development is regulated through complex epigenetic mechanisms. Histone deacetylases (HDACs) are one of the many layers of epigenetic modulation, whereby they remove acetylation marks on histone tails, prompting chromatin tightening and therefore bring about gene repression. The most extensively characterised HDACs in cardiac development are HDACs 1–3, all belonging to the Class I HDAC family. Global as well as tissue-specific knockout models in mice have provided insight into the phenotypes generated by loss of these key molecular regulators. In some instances, molecular processes that individual HDACs regulate within cardiac development have also been revealed, although the epigenetic targets and binding partners of HDACs within cardiac development are still relatively understudied. Knowledge has also been contributed from in vitro studies using stem cell-derived models as well as burgeoning research using the zebrafish model. The aim of this review is to summarise the current knowledge of class I HDAC function during key stages of cardiac development, including cardiac specification and differentiation, looping morphogenesis, and second heart field development. The role of class I HDACs in non-cardiomyocyte populations, such as the endocardium, valves, and epicardium is also discussed.
心脏发育过程中的基因表达受复杂的表观遗传机制调控。组蛋白去乙酰化酶(hdac)是许多层表观遗传调节中的一层,它们去除组蛋白尾部的乙酰化标记,促使染色质收紧,从而导致基因抑制。在心脏发育中最广泛表征的HDAC是HDAC 1-3,它们都属于I类HDAC家族。小鼠的全局和组织特异性敲除模型提供了对这些关键分子调节因子缺失所产生的表型的见解。在某些情况下,个别hdac调节心脏发育的分子过程也已被揭示,尽管hdac在心脏发育中的表观遗传靶点和结合伙伴的研究仍然相对不足。使用干细胞衍生模型的体外研究以及使用斑马鱼模型的新兴研究也贡献了知识。本综述的目的是总结目前对心脏发育关键阶段I类HDAC功能的了解,包括心脏规范和分化,环形态发生和第二心野发育。I类hdac在非心肌细胞群(如心内膜、瓣膜和心外膜)中的作用也进行了讨论。
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引用次数: 0
Dynamical systems of fate and form in development 发展中的命运和形式的动力系统
IF 6.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-01 Epub Date: 2025-06-03 DOI: 10.1016/j.semcdb.2025.103620
Alex M. Plum, Mattia Serra
Developmental biology has long drawn on dynamical systems to understand the diverging fates and the emerging form of the developing embryo. Cell differentiation and morphogenesis unfold in high-dimensional gene-expression spaces and position spaces. Yet, their stable and reproducible outcomes suggest low-dimensional geometric structures—e.g., fixed points, manifolds, and dynamic attracting and repelling structures—that organize cell trajectories in both spaces. This review surveys the history and recent advances in dynamical systems frameworks for development. We focus on techniques for extracting the organizing geometric structures of cell fate decisions and morphogenetic movements from experiments, as well as their interconnections. This unifying, dynamical systems perspective aids in rationalizing increasingly complex experimental datasets, facilitating principled dimensionality reduction and an integrated understanding of development, bridging typically distinct domains.
发育生物学长期以来一直利用动力系统来理解发育胚胎的分化命运和新兴形式。细胞的分化和形态发生在高维的基因表达空间和位置空间中展开。然而,他们的稳定和可重复的结果表明低维几何结构-例如。,固定点,流形,以及动态吸引和排斥结构,这些结构组织了两个空间中的细胞轨迹。本文综述了动力系统发展框架的历史和最新进展。我们专注于从实验中提取细胞命运决定和形态发生运动的组织几何结构的技术,以及它们的相互联系。这种统一的动态系统视角有助于使日益复杂的实验数据集合理化,促进原则性的降维和对发展的综合理解,连接典型的不同领域。
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引用次数: 0
A case study of agent-based modeling of cytoskeletal processes 基于agent的细胞骨架过程建模案例研究
IF 6.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-01 Epub Date: 2025-07-02 DOI: 10.1016/j.semcdb.2025.103625
Daniel B. Cortes
Modern cell and developmental biologists have access to a wide range of tools in microscopy, genetics, and molecular biology that enable the design of experiments that test hypotheses previously thought untestable or inaccessible. Still, even with the most recent advancements in technique and technology, some hypotheses remain just out of reach by in vivo and in vitro experimentation alone. Mathematical modeling is a long-standing method for the exploration of the physical sciences, chemistry and physics, and has provided significant insights into biological processes across all scales of life, from the modeling of population dynamics to the modeling of protein folding and molecular interactions. In this review, I highlight a specific subset of mathematical models – agent-based models, which explicitly simulate individual proteins or protein complexes and their physical interactions with each other within a simulated cellular environment. This review provides two specific case studies, from my own research efforts, which provide direct examples of how a cell biologist can develop mathematical models that complement their research efforts and help drive the generation of new ideas, or test hypotheses that cannot easily be tested through biological methods alone.
现代细胞和发育生物学家可以使用显微镜、遗传学和分子生物学中的各种工具,这些工具可以设计实验来测试以前认为无法测试或无法实现的假设。然而,即使有了最新的技术进步,一些假设仍然无法通过体内和体外实验来实现。数学建模是探索物理科学、化学和物理的一种长期方法,并为从种群动力学建模到蛋白质折叠和分子相互作用建模的所有生命尺度的生物过程提供了重要的见解。在这篇综述中,我强调了数学模型的一个特定子集-基于主体的模型,它明确地模拟单个蛋白质或蛋白质复合物及其在模拟细胞环境中的物理相互作用。这篇综述提供了两个具体的案例研究,它们来自我自己的研究工作,它们提供了一个细胞生物学家如何开发数学模型来补充他们的研究工作,并帮助推动新想法的产生,或者测试无法通过单独的生物学方法轻松测试的假设的直接例子。
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引用次数: 0
Ploidy in cardiovascular development and regeneration 心血管发育和再生的倍性
IF 6.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-01 Epub Date: 2025-05-20 DOI: 10.1016/j.semcdb.2025.103618
Tian Lan , Sabrina Kaminsky , Chi-Chung Wu
Somatic polyploidy, a non-inheritable form of genome multiplication, plays cell-type specific and context-dependent roles in organ development and regeneration. In the mammalian heart, embryonic cardiomyocytes are primarily diploid, which lose their ability to complete cell division and become polyploid as they mature. Unlike lower vertebrates like zebrafish, polyploid cardiomyocytes are commonly found across mammals, including humans. Intriguingly, the degree, timing, and modes of cardiomyocyte polyploidization vary greatly between species. In addition to the association with cardiomyocyte development and maturation, recent studies have established polyploidy as a barrier against cardiomyocyte proliferation and heart regeneration following cardiac injury. Hence, a thorough understanding of how and why cardiomyocyte become polyploid will provide insights into heart development and may help develop therapeutic strategies for heart regeneration. Here, we review the dynamics of cardiomyocyte polyploidization across species and how cardiomyocyte-intrinsic, -extrinsic, and environmental factors regulate this process as well as the impact of cardiomyocyte polyploidization on heart development and regeneration.
体细胞多倍体是一种非遗传的基因组增殖形式,在器官发育和再生中起着细胞类型特异性和环境依赖性的作用。在哺乳动物心脏中,胚胎心肌细胞主要是二倍体,当它们成熟时失去完成细胞分裂的能力而变成多倍体。与斑马鱼等低等脊椎动物不同,多倍体心肌细胞在包括人类在内的哺乳动物中普遍存在。有趣的是,不同物种之间心肌细胞多倍体化的程度、时间和模式差异很大。除了与心肌细胞的发育和成熟有关外,最近的研究已经确定多倍体是心脏损伤后心肌细胞增殖和心脏再生的屏障。因此,彻底了解心肌细胞如何以及为什么会变成多倍体将为心脏发育提供见解,并可能有助于制定心脏再生的治疗策略。在这里,我们回顾了跨物种心肌细胞多倍体化的动力学,以及心肌细胞内在、外在和环境因素如何调节这一过程,以及心肌细胞多倍体化对心脏发育和再生的影响。
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引用次数: 0
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Seminars in cell & developmental biology
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