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In vitro modeling of cell types in cardiogenesis and congenital heart disease 心脏发生和先天性心脏病细胞类型的体外建模。
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-29 DOI: 10.1016/j.semcdb.2025.103656
Sanjeev S. Ranade
Congenital heart defects (CHD) are present in nearly 1 % of live births and are a leading cause of infant mortality. Despite advances in genome sequencing technologies and an increased understanding of the genes necessary for heart development, the etiology of a majority of CHD cases remains undefined. Recent breakthroughs in single-cell genomics, lineage tracing, and live imaging in animal models of cardiogenesis have revealed the precise spatiotemporal dynamics of discrete cell types in heart development. Here, I review how these findings have informed the development of new human pluripotent stem cell methods to generate a diverse range of cells in cardiogenesis. A key unifying theme is that multipotent cardiac progenitor cells are extraordinarily responsive to slight changes to signaling factors administered at various stages of cardiac differentiation. I highlight how the ability to make a range of cardiac cell types can be used to define context specific mechanisms of CHD. I then describe how in vitro human models of cardiogenesis are especially important in cases of severe forms of CHD, such as single ventricle disorders, for which the complex genetic underlying mechanisms are poorly defined and animal models are lacking.
先天性心脏缺陷(CHD)存在于近1 %的活产婴儿中,是婴儿死亡的主要原因。尽管基因组测序技术取得了进步,对心脏发育所需基因的了解也有所增加,但大多数冠心病病例的病因仍不明确。最近在单细胞基因组学、谱系追踪和心脏发生动物模型的实时成像方面的突破揭示了心脏发育中离散细胞类型的精确时空动态。在这里,我回顾了这些发现如何为新的人类多能干细胞方法的发展提供信息,以在心脏发生中产生多种细胞。一个关键的统一主题是,多能性心脏祖细胞对在心脏分化的各个阶段给予的信号因子的轻微变化具有非凡的反应。我强调了如何利用制造一系列心脏细胞类型的能力来定义冠心病的特定机制。然后,我描述了体外心脏发生的人类模型在严重形式的冠心病(如单心室疾病)的情况下是如何特别重要的,因为复杂的遗传潜在机制尚未明确,而且缺乏动物模型。
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引用次数: 0
Viscoelasticity during development: What is it? and why should you care? 开发过程中的粘弹性:什么是粘弹性?你为什么要在意呢?
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-27 DOI: 10.1016/j.semcdb.2025.103655
Yicheng Dong , Spandan Maiti , Lance A. Davidson
Viscoelasticity is a fundamental feature of biological tissues and plays a vital role in cells and tissues. This review explores the role of viscoelasticity in mechanobiology, emphasizing its impact on morphogenesis and organogenesis during embryonic development. We discuss the viscoelastic behavior of cells and tissues and its role in how cells and tissues absorb, dissipate, and transmit mechanical energy. We summarize experimental techniques such as Atomic Force Microscopy (AFM), Micropipette Aspiration (MA), and Tissue Stretchers, that have been used to quantify or observe the effects of viscoelasticity. Mathematical models of viscoelasticity, such as the Standard Linear Solid (SLS) model and advanced fractional models are introduced and discussed for their ability to capture the complexity of the viscoelastic behavior of biological systems. The role of subcellular complexes, including the cytoskeleton, extracellular matrix, and nucleus, are also reviewed for their contributions to tissue viscoelastic behavior. We also identify and discuss knowledge gaps, particularly in understanding how dynamic mechanical cues influence viscoelastic responses across cellular and tissue scales. A deeper exploration of these mechanisms, particularly those that determine viscoelastic behavior of cells and tissues, is needed for advancing our understanding of embryonic development and tissue morphogenesis.
粘弹性是生物组织的基本特征,在细胞和组织中起着至关重要的作用。本文综述了粘弹性在力学生物学中的作用,重点介绍了粘弹性在胚胎发育过程中对形态发生和器官发生的影响。我们讨论细胞和组织的粘弹性行为及其在细胞和组织如何吸收、消散和传递机械能中的作用。我们总结了实验技术,如原子力显微镜(AFM),微吸管抽吸(MA)和组织拉伸器,已用于量化或观察粘弹性的影响。粘弹性的数学模型,如标准线性固体(SLS)模型和先进的分数模型被介绍和讨论,因为它们能够捕捉生物系统粘弹性行为的复杂性。亚细胞复合物的作用,包括细胞骨架、细胞外基质和细胞核,也回顾了它们对组织粘弹性行为的贡献。我们还识别和讨论知识差距,特别是在理解动态机械线索如何影响细胞和组织尺度上的粘弹性反应方面。我们需要对这些机制,特别是那些决定细胞和组织粘弹性行为的机制进行更深入的探索,以促进我们对胚胎发育和组织形态发生的理解。
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引用次数: 0
The interplay of tissue mechanics and gene regulatory networks in the evolution of morphogenesis 组织力学和基因调控网络在形态发生进化中的相互作用
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-26 DOI: 10.1016/j.semcdb.2025.103654
James DiFrisco, Rashmi Priya
Recent years have seen the growth of work illuminating the mechanical aspects of morphogenesis, but its relationship to the established ideas and evidence of developmental and evolutionary genetics remains enigmatic. This review aims to re-assess the conceptual relationship between mechanics and genetics in the context of animal morphogenesis. We propose a view in which genetic programs—understood as gene regulatory networks—and processes of physical self-organization are not conflicting models of development, but instead play necessary and complementary causal roles at cellular and supra-cellular length scales, respectively. Current evidence from evolutionary genetics supports the hypothesis that this form of complementarity may be necessary for morphogenesis to be evolvable.
近年来,关于形态发生的机械方面的研究越来越多,但它与发育和进化遗传学的既定观点和证据的关系仍然是一个谜。这篇综述旨在重新评估在动物形态发生的背景下力学和遗传学之间的概念关系。我们提出了一种观点,认为遗传程序(被理解为基因调控网络)和物理自组织过程并不是相互冲突的发展模式,而是在细胞和超细胞长度尺度上分别发挥必要和互补的因果作用。目前来自进化遗传学的证据支持这样的假设,即这种形式的互补可能是形态发生进化所必需的。
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引用次数: 0
Zebrafish as a model system for studying cilia biology and ciliopathies 斑马鱼作为研究纤毛生物学和纤毛病的模型系统
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-25 DOI: 10.1016/j.semcdb.2025.103652
Mengfan Wu , Jiongchen Lin , Chengjie Yu , Chengtian Zhao , Haibo Xie
Cilia are highly conserved, microtubule-based, hair-like organelles that project from the surface of most eukaryotic cells. They perform essential functions in signal transduction, cellular motility, and the regulation of fluid flow within tissues. Foundational insights into ciliary biology have largely been derived from invertebrate models such as Chlamydomonas reinhardtii and Caenorhabditis elegans, which each possess a relatively uniform cilium type. In contrast, vertebrates display remarkable diversity in ciliary subtypes, with distinct structures and functions tailored to specific tissues. This diversity underlies the broad physiological importance of cilia, and it also explains why defects in ciliary assembly or function result in a wide spectrum of human genetic disorders collectively known as ciliopathies. As a result, vertebrate models have become indispensable for uncovering the roles of cilia in both normal development and disease pathogenesis. Among them, zebrafish has emerged as a particularly versatile and powerful model system. Its unique experimental advantages—including optical transparency during embryogenesis, external fertilization, high fecundity, and compatibility with large-scale genetic and pharmacological screening—make it ideally suited for studying ciliary biology in vivo. In this review, we summarize recent advances in our understanding of ciliary function using zebrafish, with particular emphasis on studies of ciliopathy-associated genes and newly uncovered roles of cilia in processes such as spinal development and meiosis. Finally, we discuss current challenges and outline future research directions, highlighting how zebrafish will continue to drive discoveries in cilia biology and ciliopathy research.
纤毛是一种高度保守的、基于微管的、毛发状的细胞器,从大多数真核细胞表面伸出。它们在信号转导、细胞运动和组织内流体流动的调节中发挥重要作用。对纤毛生物学的基本认识在很大程度上来源于无脊椎动物模型,如莱茵衣藻和秀丽隐杆线虫,它们都具有相对统一的纤毛类型。相比之下,脊椎动物在纤毛亚型中表现出显著的多样性,具有针对特定组织的独特结构和功能。这种多样性奠定了纤毛广泛的生理重要性,也解释了为什么纤毛组装或功能缺陷导致广泛的人类遗传疾病,统称为纤毛病。因此,脊椎动物模型已成为揭示纤毛在正常发育和疾病发病机制中的作用不可或缺的工具。其中,斑马鱼已经成为一个特别通用和强大的模型系统。其独特的实验优势-包括胚胎发生时的光学透明性,体外受精,高繁殖力,以及与大规模遗传和药理筛选的兼容性-使其非常适合体内研究纤毛生物学。在这篇综述中,我们总结了近年来我们对斑马鱼纤毛功能的理解,特别强调了纤毛病相关基因的研究以及新发现的纤毛在脊柱发育和减数分裂等过程中的作用。最后,我们讨论了当前的挑战并概述了未来的研究方向,强调斑马鱼将如何继续推动纤毛生物学和纤毛病研究的发现。
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引用次数: 0
Lessons for cardiac regeneration from non-mammalian model organisms 非哺乳动物模式生物心脏再生的经验教训。
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-18 DOI: 10.1016/j.semcdb.2025.103653
Yusuke Watanabe, Kazu Kikuchi
Unlike mammals, certain non-mammalian species — such as amphibians and teleost fish — can regenerate their hearts after severe damage. Investigating non-mammalian heart regeneration could provide strategies to reactivate regenerative mechanisms in adult human hearts, potentially reducing morbidity and mortality related to heart failure. This review offers an overview of key findings from earlier studies using amphibian models and highlights recent advances from teleost fish, with a particular focus on signaling pathways, enhancers, and transcription factors that regulate the endogenous mechanisms of cardiac regeneration.
与哺乳动物不同,某些非哺乳动物物种,如两栖动物和硬骨鱼,在严重损伤后可以再生心脏。研究非哺乳动物心脏再生可以为重新激活成人心脏再生机制提供策略,有可能降低与心力衰竭相关的发病率和死亡率。本文综述了早期使用两栖动物模型研究的主要发现,并重点介绍了硬骨鱼的最新进展,特别关注调节心脏再生内源性机制的信号通路、增强子和转录因子。
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引用次数: 0
Chlamydomonas as a model system for the study of cilia and eukaryotic flagella 衣单胞菌作为研究纤毛和真核鞭毛的模式系统。
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-18 DOI: 10.1016/j.semcdb.2025.103658
Xuecheng Li , Qingqing Liu , Junmin Pan
Chlamydomonas is a haploid, unicellular green alga that serves as an excellent model system for studying ciliary biology. It possesses two motile cilia of equal length, making it ideal for investigating both ciliogenesis and ciliary motility, as well as cilia-based signaling. The organism's ease of cultivation, the simplicity of cilia isolation, and the availability of well-established experimental systems for rapid and synchronous cilia regeneration and disassembly contribute to its utility in laboratory research. Furthermore, Chlamydomonas is highly amenable to a variety of genetic approaches, enhancing its value as a model organism. Due to the high degree of conservation in the core mechanisms governing ciliary structure and function, discoveries made in Chlamydomonas have significantly advanced our understanding of cilia across species and have provided important insights into cilia-related human disorders. In this overview, we summarize the key cellular features, life cycle stages, ciliary architecture and dynamics, ciliary behavior, biochemical and genetic advantages of Chlamydomonas as a model organism. Our goal is to provide a foundational perspective for those new to ciliary research in Chlamydomonas - including early-career scientists, experienced researchers transitioning from other fields, and cilia experts working with alternative model systems.
衣藻是一种单细胞的单倍体绿藻,是研究纤毛生物学的一个很好的模型系统。它具有两个相同长度的运动纤毛,使其成为研究纤毛发生和纤毛运动性以及纤毛信号传导的理想工具。该生物易于培养,纤毛分离简单,以及建立完善的实验系统可用于快速和同步的纤毛再生和拆卸,这有助于其在实验室研究中的应用。此外,衣藻高度适应各种遗传方法,提高了其作为模式生物的价值。由于控制纤毛结构和功能的核心机制高度保守,在衣单胞菌中的发现大大提高了我们对不同物种纤毛的理解,并为与纤毛相关的人类疾病提供了重要的见解。本文综述了衣藻作为一种模式生物的主要细胞特征、生命周期阶段、纤毛结构和动力学、纤毛行为、生化和遗传优势。我们的目标是为那些新的衣藻纤毛研究提供一个基础的观点-包括早期职业科学家,从其他领域过渡的经验丰富的研究人员,以及使用替代模型系统的纤毛专家。
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引用次数: 0
Mammalian motile cilia: Structure, formation, organization, and function 哺乳动物活动纤毛:结构、形成、组织和功能
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-06 DOI: 10.1016/j.semcdb.2025.103651
Xueliang Zhu
Cilia are membrane-covered hair-like organelles built on specialized centrioles and conserved throughout eukaryotic evolution. They are either motile or immotile, serving respectively as versatile signaling antennae or elegant beating nanomachines. Accordingly, their dysfunctions cause a wide variety of developmental and degenerative disorders, which in human are syndromes termed ciliopathies. Motile cilia in mammals reside in epithelial cells. Their rapid, rhythmic beating facilitates reproduction, left-right patterning, and organ homeostasis by propelling directional gamete transport, nodal flow, cerebrospinal fluid circulation, and mucus clearance. They merge mostly as multicilia, with up to hundreds per cell. Multiciliated cells need not only to break the tight cellular control on centriole biogenesis and ensure accurate assemblies of numerous structural components for their formations, but to properly organize and polarize them for their functions as well. This review mainly focuses on the cell biology of mammalian motile cilia, with the mouse as the model organism.
纤毛是一种被膜覆盖的毛发状细胞器,建立在特殊的中心粒上,在真核生物的进化过程中一直保存着。它们要么是活动的,要么是不活动的,分别充当多功能信号天线或优雅的跳动纳米机器。因此,它们的功能障碍引起各种各样的发育和退行性疾病,这些疾病在人类中被称为纤毛病。哺乳动物的活动纤毛存在于上皮细胞中。它们快速、有节奏的跳动通过促进定向配子运输、淋巴结流动、脑脊液循环和粘液清除来促进生殖、左右模式和器官稳态。它们大多合并成多毛细胞,每个细胞多达数百个。多毛细胞不仅需要打破细胞对中心粒生物发生的严格控制,确保其形成的众多结构成分的精确组装,而且需要正确组织和极化它们以实现其功能。本文以小鼠为模型生物,对哺乳动物运动纤毛的细胞生物学进行了综述。
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引用次数: 0
Decoding zebrafish oogenesis: From primordial germ cell development to fertilization 解码斑马鱼的卵发生:从原始生殖细胞发育到受精
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-05 DOI: 10.1016/j.semcdb.2025.103650
Laura Hofmann, Carl-Philipp Heisenberg
Oogenesis – the formation and development of an oocyte – is fundamental to reproduction and embryonic development. Due to its accessibility to genetic manipulations and the ability to culture and experimentally manipulate oocytes ex vivo, zebrafish has emerged as a powerful vertebrate model system for studying oogenesis. In this review, we provide a comprehensive overview of zebrafish oogenesis, from early germ cell formation to oocyte maturation and fertilization. We discuss recent advances in uncovering the molecular and cellular mechanisms driving this complex process and highlight key knowledge gaps that remain to be addressed.
卵发生-卵母细胞的形成和发育-是生殖和胚胎发育的基础。由于其易于遗传操作和体外培养和实验操作卵母细胞的能力,斑马鱼已成为研究卵子发生的强大脊椎动物模型系统。在这篇综述中,我们提供了斑马鱼卵发生的全面概述,从早期生殖细胞形成到卵母细胞成熟和受精。我们讨论了在揭示驱动这一复杂过程的分子和细胞机制方面的最新进展,并强调了仍有待解决的关键知识空白。
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引用次数: 0
Approximating the living 贴近生活
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-01 DOI: 10.1016/j.semcdb.2025.103646
Rob Phillips
Is a herd of wildebeest better thought of as a series of individual animals, each with its own glorious and unmanageable volition, or as a field of moving arrows? Are the morphogen gradients that set up the coordinate systems for embryonic anterior–posterior patterning a smooth and continuous concentration field or instead a chaotic collection of protein molecules each jiggling about in the haphazard way first described by Robert Brown in his microscopical observations of pollen? Is water, the great liquid ether of the living world, a collection of discrete molecules or instead a perfectly continuous medium with a density of 1000 kg/m3? In this article, I will argue that these questions pose a false dichotomy since there are many different and powerful representations of the world around us. Different representations suit us differently at different times and it is often useful to be able to hold these seemingly contradictory notions in our heads simultaneously. Indeed, mathematics is not only the language of representation, but often is also the engine of reconciliation of such disparate views. In a letter to Alfred Russel Wallace on 14 April 1869, Charles Darwin noted that Lord Kelvin’s “views on the recent age of the world have been for some time one of my sorest troubles”. Here, I will argue that one of the highest attainments of the scientific enterprise is a coherent picture of the world, a picture in which our stories about the geological age of the Earth are coherent with our stories of how whales populated the oceans, our understanding of the living jibes with our understanding of the inanimate, our insights into the dynamics of genes and molecular structures are consonant with our physical understanding of the laws of statistical physics. The underpinnings of such coherency are often best revealed when viewed through the lens of mathematics.
一群角马应该被看作是一系列独立的动物,每只动物都有自己辉煌而难以控制的意志,还是一大片移动的箭?为胚胎前后模式建立坐标系统的形态发生梯度是一个平滑而连续的浓度场,还是像罗伯特·布朗在他对花粉的显微镜观察中首次描述的那样,是一组杂乱无章的蛋白质分子,每个分子都以随意的方式摇摆?水,生命世界中最伟大的液体醚,是离散分子的集合,还是密度为≈1000kg /m3的完美连续介质?在这篇文章中,我将论证这些问题构成了一个错误的二分法,因为我们周围的世界有许多不同且强大的表征。不同的表象在不同的时间适合我们,能够同时在我们的头脑中持有这些看似矛盾的概念通常是有用的。事实上,数学不仅是表达的语言,而且常常是调和这些不同观点的引擎。1869年4月14日,查尔斯·达尔文在给阿尔弗雷德·罗素·华莱士的一封信中指出,开尔文勋爵“对近代世界的看法一度是我最头疼的问题之一”。在这里,我想说的是,科学事业的最高成就之一是一幅连贯的世界图景,在这幅图景中,我们关于地球地质年代的故事与我们关于鲸鱼如何在海洋中繁衍的故事是一致的,我们对生物的理解与我们对无生命的理解是一致的,我们对基因和分子结构动力学的见解与我们对统计物理定律的物理理解是一致的。从数学的角度来看,这种一致性的基础往往是最好的揭示。
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引用次数: 0
Biophysical, cellular, and mouse model approaches to investigate the mechanical regulation of folliculogenesis 生物物理,细胞和小鼠模型方法来研究卵泡发生的机械调节
IF 6 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-30 DOI: 10.1016/j.semcdb.2025.103649
Sara Pietroforte, Farners Amargant
Folliculogenesis, which is the process by which ovarian follicles develop to support oogenesis and hormone production, is essential for female fertility. Although hormonal and biochemical signaling pathways regulating folliculogenesis have been extensively studied, increasing evidence suggests that mechanical cues within the ovary also play a critical role. The ovary is composed of follicles, corpora lutea, and stroma, each contributing to a biomechanical microenvironment that might change across the reproductive lifespan. Additionally, the spatial organization of the ovary, with a collagen-rich cortex and a softer medulla, may influence follicle activation and growth. This review explores the hypothesis that mechanical properties of the ovary regulate folliculogenesis, integrating current knowledge on ovarian architecture, extracellular matrix composition, and mechanotransduction pathways. We highlight recent findings supporting mechanical regulation of folliculogenesis, discuss contradictory data, and describe the tools and models used to investigate this concept. By considering mechanical forces alongside hormonal and biochemical signals, we propose a more integrated view of the factors governing follicle development, with implications for understanding ovarian physiology and pathology.
卵泡发生是指卵巢卵泡发育以支持卵子发生和激素产生的过程,对女性生育能力至关重要。虽然调节卵泡发生的激素和生化信号通路已被广泛研究,但越来越多的证据表明卵巢内的机械信号也起着关键作用。卵巢由卵泡、黄体和基质组成,每一个组成的生物力学微环境都可能在整个生殖周期中发生变化。此外,卵巢的空间组织,胶原蛋白丰富的皮层和柔软的髓质,可能影响卵泡的激活和生长。本文结合目前关于卵巢结构、细胞外基质组成和机械转导途径的知识,探讨了卵巢的机械特性调节卵泡发生的假设。我们重点介绍了支持卵泡发生机械调节的最新发现,讨论了相互矛盾的数据,并描述了用于研究这一概念的工具和模型。通过考虑机械力以及激素和生化信号,我们提出了一个更综合的卵泡发育控制因素的观点,这对理解卵巢生理和病理具有重要意义。
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引用次数: 0
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Seminars in cell & developmental biology
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