Seminars in cell & developmental biology最新文献

英文中文

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

Seminars in cell & developmental biology

Pub 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

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

Seminars in cell & developmental biology

Pub 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

Agent-based modeling of complex molecular mechanisms 基于agent的复杂分子机制建模

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-06-17 DOI: 10.1016/j.semcdb.2025.103626

Margot Riggi , Janet H. Iwasa

The diverse molecular mechanisms that orchestrate cellular processes typically involve a complex network of actors and span broad ranges of spatial and temporal scales that no single experimental or computational technique can cover. While several multiscale methods are increasingly capable of connecting across scales, bridging molecular and cellular levels remains a challenge. Agent-based modeling (ABM) is a computational paradigm that models a complex system and its emergent properties from the perspective of its individual components whose behaviors are governed by a set of predefined rules. As long as these rules are biophysically accurate, the flexibility of this framework makes it uniquely positioned to fill the gap between spatially detailed and computationally efficient approaches and emerge as an effective mesoscopic modeling method that could bring valuable mechanistic insight into how complex behaviors arise in cellular environments. In this review, we summarize ABM principles and current capabilities in the realm of molecular biology and discuss potential directions for the development of additional features that would further broaden the scope of the method.

协调细胞过程的不同分子机制通常涉及复杂的参与者网络，跨越广泛的空间和时间尺度，这是单一的实验或计算技术无法覆盖的。虽然几种多尺度方法越来越有能力跨尺度连接，桥接分子和细胞水平仍然是一个挑战。基于代理的建模（ABM）是一种计算范式，它从单个组件的角度对复杂系统及其紧急属性进行建模，这些组件的行为受一组预定义规则的控制。只要这些规则在生物物理上是准确的，该框架的灵活性使其具有独特的定位，可以填补空间细节和计算效率方法之间的空白，并作为一种有效的介观建模方法出现，可以为细胞环境中复杂行为的产生带来有价值的机制见解。在这篇综述中，我们总结了ABM的原理和目前在分子生物学领域的能力，并讨论了潜在的发展方向，以进一步扩大该方法的范围。

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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

Seminars in cell & developmental biology

Pub 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

Cardiac trabeculation in vertebrates: Convergent evolution or evolutionary adaptations associated with heart complexity? 脊椎动物心脏小梁：趋同进化还是与心脏复杂性相关的进化适应？

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-06-05 DOI: 10.1016/j.semcdb.2025.103622

Yen T.H. Tran , Diptarka Saha , Gonzalo del Monte-Nieto

One of the most important processes during early heart development is the formation of trabecular myocardium. Cardiac trabeculation is the process by which the ventricular chambers develop a complex sponge-like myocardium essential for optimal cardiac function to provide efficient oxygenation and nourishment to the developing embryo. Indeed, its importance is highlighted by the fact that defects in trabecular formation lead to embryonic lethality and congenital heart disease. In the last decades, our understanding of cardiac trabeculation in different vertebrate models has advanced significantly. However, instead of reinforcing cardiac trabeculation as a highly evolutionarily conserved process across vertebrates, these studies have identified significant differences in the way the process occurs and how it is regulated in different vertebrate species. In this review, we assembled the current knowledge on cardiac trabeculation in different vertebrate species and examined if trabecular myocardium development can be achieved through different morphogenetic processes across vertebrates or if these differences are associated with evolutionary adaptations required to develop more complex vertebrate hearts.

早期心脏发育过程中最重要的过程之一是小梁心肌的形成。心脏小梁是心室形成复杂的海绵状心肌的过程，这是最佳心脏功能所必需的，为发育中的胚胎提供有效的氧合和营养。事实上，小梁形成缺陷导致胚胎死亡和先天性心脏病的事实突出了它的重要性。在过去的几十年里，我们对不同脊椎动物模型的心脏小梁的理解有了显著的进步。然而，这些研究并没有将心脏小梁作为一种高度进化保守的过程在脊椎动物中得到加强，而是发现了该过程在不同脊椎动物物种中发生的方式及其调节方式的显著差异。在这篇综述中，我们收集了目前关于不同脊椎动物心脏小梁的知识，并研究了小梁心肌的发育是否可以通过不同的脊椎动物的形态发生过程来实现，或者这些差异是否与发展更复杂的脊椎动物心脏所需的进化适应有关。

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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

Seminars in cell & developmental biology

Pub 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。

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

Seminars in cell & developmental biology

Pub 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

Cardiac regeneration: Unraveling the complex network of intercellular crosstalk 心脏再生：揭示细胞间串扰的复杂网络

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-05-13 DOI: 10.1016/j.semcdb.2025.103619

Bailin Wu , Florian Constanty , Arica Beisaw

The heart is composed of multiple cell types, including cardiomyocytes, endothelial/endocardial cells, fibroblasts, resident immune cells and epicardium and crosstalk between these cell types is crucial for proper cardiac function and homeostasis. In response to cardiac injury or disease, cell-cell interactions and intercellular crosstalk contribute to remodeling to compensate reduced heart function. In some vertebrates, the heart can regenerate following cardiac injury. While cardiomyocytes play a crucial role in this process, additional cell types are necessary to create a pro-regenerative microenvironment in the injured heart. Here, we review recent literature regarding the importance of cellular crosstalk in promoting cardiac regeneration and provide insight into emerging technologies to investigate cell-cell interactions in vivo. Lastly, we explore recent studies highlighting the importance of inter-organ communication in response to injury and promotion of cardiac regeneration. Importantly, understanding how intercellular and inter-organ crosstalk promote cardiac regeneration is essential for the development of therapeutic strategies to stimulate regeneration in the human heart.

心脏由多种细胞类型组成，包括心肌细胞、内皮/心内膜细胞、成纤维细胞、常驻免疫细胞和心外膜，这些细胞类型之间的相互作用对心脏正常功能和稳态至关重要。在对心脏损伤或疾病的反应中，细胞间的相互作用和细胞间的串扰有助于重塑以补偿心脏功能的降低。在一些脊椎动物中，心脏损伤后可以再生。虽然心肌细胞在这一过程中起着至关重要的作用，但还需要其他类型的细胞来在受伤的心脏中创造一个促进再生的微环境。在这里，我们回顾了最近关于细胞串扰在促进心脏再生中的重要性的文献，并提供了研究体内细胞-细胞相互作用的新兴技术的见解。最后，我们探讨了最近的研究，强调了器官间通讯在响应损伤和促进心脏再生中的重要性。重要的是，了解细胞间和器官间的串扰如何促进心脏再生对于开发刺激人类心脏再生的治疗策略至关重要。

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引用次数: 0

A near death experience: The secret stem cell life of caspase-3 濒死体验：caspase-3干细胞生命的秘密

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-05-08 DOI: 10.1016/j.semcdb.2025.103617

Mahasen Sarji , Roi Ankawa , Matan Yampolsky , Yaron Fuchs

Caspase-3 is known to play a pivotal role in mediating apoptosis, a key programmed cell death pathway. While extensive research has focused on understanding how caspase-3 is activated and functions during apoptosis, emerging evidence has revealed its significant non-apoptotic roles across various cell types, including stem cells. This review explores the critical involvement of caspase-3 in regulating stem cell properties, maintaining stem cell populations, and facilitating tissue regeneration. We also explore the potential pathological consequences of caspase-3 dysfunction in stem cells and cancer cells alongside the therapeutic opportunities of targeting caspase-3.

已知Caspase-3在介导细胞凋亡（一种关键的程序性细胞死亡途径）中起关键作用。虽然广泛的研究集中在了解caspase-3在细胞凋亡过程中的激活和功能，但新出现的证据表明，它在包括干细胞在内的各种细胞类型中具有重要的非凋亡作用。这篇综述探讨了caspase-3在调节干细胞特性、维持干细胞群和促进组织再生中的关键作用。我们还探讨了caspase-3在干细胞和癌细胞中功能障碍的潜在病理后果以及靶向caspase-3的治疗机会。

引用次数: 0

Artery regeneration: Molecules, mechanisms and impact on organ function 动脉再生：分子、机制及对器官功能的影响

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-05-02 DOI: 10.1016/j.semcdb.2025.103611

Swarnadip Ghosh , Bhavnesh Bishnoi , Soumyashree Das

Replenishment of artery cells to repair or create new arteries is a promising strategy to re-vascularize ischemic tissue. However, limited understanding of cellular and molecular programs associated with artery (re-)growth impedes our efforts towards designing optimal therapeutic approaches. In this review, we summarize different cellular mechanisms that drive injury-induced artery regeneration in distinct organs and organisms. Artery formation during embryogenesis includes migration, self-amplification, and changes in cell fates. These processes are coordinated by multiple signaling pathways, like Vegf, Wnt, Notch, Cxcr4; many of which, also involved in injury-induced vascular responses. We also highlight how physiological and environmental factors determine the extent of arterial re-vascularization. Finally, we discuss different in vitro cellular reprogramming and tissue engineering approaches to promote artery regeneration, in vivo. This review provides the current understanding of endothelial cell fate reprogramming and explores avenues for regenerating arteries to restore organ function through efficient revascularization.

补充动脉细胞来修复或创造新的动脉是一种很有前途的策略来重建缺血组织。然而，对与动脉（再）生长相关的细胞和分子程序的有限理解阻碍了我们设计最佳治疗方法的努力。在这篇综述中，我们总结了不同器官和生物体中驱动损伤诱导的动脉再生的不同细胞机制。胚胎发生过程中的动脉形成包括迁移、自我扩增和细胞命运的改变。这些过程由多种信号通路协调，如Vegf、Wnt、Notch、Cxcr4；其中许多也与损伤引起的血管反应有关。我们还强调了生理和环境因素如何决定动脉再血管化的程度。最后，我们讨论了不同的体外细胞重编程和组织工程方法来促进体内动脉再生。本文综述了目前对内皮细胞命运重编程的认识，并探讨了通过有效的血管再生来恢复器官功能的动脉再生途径。

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引用次数: 0

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