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Charting the cardiac landscape: Advances in spatial transcriptomics for heart biology 绘制心脏景观：心脏生物学的空间转录组学进展

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-28 DOI: 10.1016/j.semcdb.2025.103648

Elie N. Farah , Jessyka T. Diaz , Joshua Bloomekatz , Neil C. Chi

The heart is the first organ to form in the developing embryo. Throughout development, it continues to grow and function to support the maturing fetus by circulating nutrients to all of the developing organs. Defects in the spatial organization of cardiac cells can lead to congenital heart defects (CHD), which affects 1–3 % of all live births, as well as adult heart diseases. Spatial transcriptomics has revolutionized our understanding of cardiac biology by providing high-resolution maps of gene expression within intact tissue, offering insights into cellular interactions and spatial organization across the entire heart. Recent improvements have enabled precise mapping of cellular heterogeneity within developing human hearts, revealing spatially organized populations of cardiomyocytes and non-cardiomyocyte cells and key signaling pathways in cardiac morphogenesis. Studies of adult hearts post-myocardial infarction (MI) using these technologies have unraveled gene expression patterns specific to injury zones. Furthermore, multi-modal approaches combining spatial transcriptomics with epigenetic, proteomic, and functional data have expanded our understanding of cell type-specific responses and molecular mechanisms underpinning cardiac injury responses and fibrosis. Here, we describe the range of spatial transcriptomic technologies currently available and discuss the technical considerations involved in conducting spatial analyses. We further highlight the progression from early spatial mapping techniques to contemporary high-resolution, multi-modal approaches in studying cardiac tissue, underscoring how these advancements provide unprecedented insights into heart development, disease, and regeneration, and discuss future directions for applying spatial transcriptomics to address fundamental questions in cardiovascular biology and therapy.

心脏是胚胎发育过程中最先形成的器官。在整个发育过程中，它继续生长并发挥作用，通过将营养物质循环到所有发育中的器官来支持成熟的胎儿。心脏细胞空间组织的缺陷可导致先天性心脏缺陷（CHD），影响所有活产婴儿的1-3 - %，以及成人心脏病。空间转录组学通过提供完整组织内基因表达的高分辨率图谱，为整个心脏的细胞相互作用和空间组织提供了见解，彻底改变了我们对心脏生物学的理解。最近的改进已经能够精确绘制人类心脏发育中的细胞异质性，揭示心肌细胞和非心肌细胞的空间组织群体以及心脏形态发生中的关键信号通路。使用这些技术对心肌梗死后成人心脏的研究揭示了损伤区特异性的基因表达模式。此外，将空间转录组学与表观遗传学、蛋白质组学和功能数据相结合的多模式方法扩大了我们对细胞类型特异性反应和支持心脏损伤反应和纤维化的分子机制的理解。在这里，我们描述了目前可用的空间转录组学技术的范围，并讨论了进行空间分析所涉及的技术考虑。我们进一步强调了从早期空间制图技术到当代高分辨率、多模态方法在心脏组织研究中的进展，强调了这些进步如何为心脏发育、疾病和再生提供前所未有的见解，并讨论了应用空间转录组学解决心血管生物学和治疗基本问题的未来方向。

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引用次数: 0

Mechanical mechanisms of morphogenesis as potential substrates for evolutionary change 形态发生的机械机制作为进化变化的潜在底物

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-23 DOI: 10.1016/j.semcdb.2025.103645

Suhrid Ghosh , Chandrashekar Kuyyamudi , Beatrice L. Steinert , Cassandra G. Extavour

The first quarter of this century has seen a resurgence of interest in the mechanical and physical mechanisms that drive cellular behaviors in the context of morphogenesis. Far from being a new discovery, the fact that the material properties of cells and the physical forces that they exert and experience must play decisive roles in development, was an important part of the field of experimental embryology well over a century ago. Following the birth of molecular biology, and the development of live imaging approaches that can capture the dynamics of both cellular properties and materials, and the activity of genes and gene products, the current manifestation of this field promises to link mechanical and molecular genetic mechanisms. Here we review recent advances in understanding the relationships between mechanical and molecular genetic mechanisms, and suggest paths forward that could yield answers to the pressing questions of whether and how evolutionary forces act not only on functional morphologies, but also on the mechanical forces that create them.

本世纪头25年，在形态发生的背景下，对驱动细胞行为的机械和物理机制的兴趣重新抬头。细胞的物质特性以及它们所施加和经历的物理力在发育过程中一定起着决定性的作用，这一事实远非一个新发现，早在一个多世纪以前，它就是实验胚胎学领域的一个重要组成部分。随着分子生物学的诞生，以及实时成像方法的发展，可以捕捉细胞特性和材料的动态，以及基因和基因产物的活性，该领域目前的表现有望将机械和分子遗传机制联系起来。在这里，我们回顾了在理解机械和分子遗传机制之间的关系方面的最新进展，并提出了可以回答进化力是否以及如何不仅作用于功能形态，而且作用于创造它们的机械力这一紧迫问题的前进道路。

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引用次数: 0

Mechanistic modeling of mitosis: Insights from three collaborative case studies 有丝分裂的机制建模：来自三个合作案例研究的见解

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-23 DOI: 10.1016/j.semcdb.2025.103643

Jing Chen , Daniela Cimini

Mechanistic mathematical modeling has become an essential tool in modern biological research due to its powerful ability to integrate diverse data, generate hypotheses, and guide experimental design. It is particularly valuable for studying complex cellular mechanisms involving numerous interacting components. While the full dynamics of such systems usually elude direct experimental observation, modeling provides a means to integrate fragmented data with reasonable and/or informed assumptions into coherent mechanistic frameworks, simulate system behavior, and identify promising directions for further experimentation. When closely integrated with experiments, modeling can greatly accelerate progress in cell biology. However, the value of modeling is not automatic—it must be earned through careful model construction, critical interpretation of results, and thoughtful design of follow-up experiments. To demystify this process, we review three of our collaborative projects in mitosis, drawing on our experiences as a modeler and an experimentalist. We describe how the projects were initiated, why specific modeling approaches were chosen, how models were developed and refined, how model predictions guided new experiments, and how integrated modeling and experimentation led to deeper mechanistic insights. Finally, we emphasize that at the heart of every successful collaboration lies human connection. Productive cross-disciplinary communication is fundamental to bridging experimental and modeling perspectives and fully realizing the potential of integrative approaches in modern cell biology.

机械数学建模具有整合多种数据、生成假设和指导实验设计的强大能力，已成为现代生物学研究的重要工具。它对于研究涉及许多相互作用成分的复杂细胞机制特别有价值。虽然这些系统的完整动态通常无法直接实验观察，但建模提供了一种方法，可以将具有合理和/或知情假设的碎片数据整合到连贯的机制框架中，模拟系统行为，并为进一步的实验确定有希望的方向。当与实验紧密结合时，建模可以极大地促进细胞生物学的进展。然而，建模的价值不是自动产生的，它必须通过仔细的模型构建、对结果的批判性解释和后续实验的周到设计来获得。为了揭开这个过程的神秘面纱，我们回顾了我们在有丝分裂方面的三个合作项目，借鉴了我们作为建模者和实验家的经验。我们描述了项目是如何启动的，为什么选择特定的建模方法，如何开发和改进模型，模型预测如何指导新的实验，以及如何集成建模和实验导致更深层次的机制见解。最后，我们强调，每一次成功合作的核心都在于人与人之间的联系。高效的跨学科交流是连接实验和建模观点以及充分实现现代细胞生物学综合方法潜力的基础。

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引用次数: 0

The mechanics behind the Drosophila egg 果蝇卵背后的机制

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-21 DOI: 10.1016/j.semcdb.2025.103638

Megha Maria Jacob, Muriel Grammont

The formation and the development of the Drosophila egg involves multiple mechanical cross-talks between germline cells, somatic cells and the surrounding basement membrane. In this review, we discuss several development stages when the sources, as well as the roles, of mechanical forces in egg shape establishment are well defined. The examples described here illustrate the diversity of these forces as well as of the tools used to measure them and of the outcome each of them generates. We examine their contributions and their integration to morphogenesis. We discuss the limitations of our current knowledge, the importance of developing novel approaches and the support that modelling could bring to tackle some issues. One major future challenge is to understand how robustness in shaping the egg is achieved when the contributors act in different cell types and at different times. Studying Drosophila egg formation thus remains an exciting model in developmental biology as it must integrate a variety of biomechanical inputs from its environment, in addition of the biochemical signals discovered in the past.

果蝇卵的形成和发育涉及生殖细胞、体细胞和周围基膜之间的多次机械交互作用。在这篇综述中，我们讨论了几个发展阶段，当来源，以及作用，机械力在鸡蛋形状的建立是明确的。这里描述的例子说明了这些力量的多样性，以及用于测量它们的工具和它们各自产生的结果的多样性。我们研究了它们对形态发生的贡献和整合。我们讨论了我们现有知识的局限性，开发新方法的重要性以及建模可以解决一些问题的支持。未来的一个主要挑战是了解当贡献者在不同的细胞类型和不同的时间活动时，如何实现塑造卵子的稳健性。因此，研究果蝇卵的形成在发育生物学中仍然是一个令人兴奋的模型，因为除了过去发现的生化信号外，它还必须整合来自环境的各种生物力学输入。

引用次数: 0

Mechanics of oogenesis: Lessons from C. elegans germline cysts 卵发生机制：秀丽隐杆线虫种系囊肿的教训

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-21 DOI: 10.1016/j.semcdb.2025.103644

Kenji Kimura, Fumio Motegi

Germ cells are organized into a syncytial architecture, wherein individual cells remain connected via intercellular bridges. Within this structural framework, known as germline cysts, a subset of germ cells enlarges and develops into oocytes, while others shrink and are eliminated through cell death. Recent studies with Caenorhabditis elegans have revealed that both apoptosis-mediated germ cell death and enlargement of surviving germ cells are regulated by mechanical forces. Germ cells exhibit stochastic fluctuations in volume driven by actomyosin contractility. This initial size heterogeneity is progressively amplified due to mechanical instability driven by differential hydrostatic pressure within the cyst, which biases smaller cells toward shrinkage and subsequent apoptotic death. This mechanical instability is further reinforced by the RAS/MAPK signaling cascade and the ECT-2/RhoA pathway, both of which enhance actomyosin contractility. Surviving germ cells continue to grow by acquiring the cytoplasmic materials through actomyosin contractility-mediated hydrodynamic flow within the cyst. Collectively, these findings highlight the critical role of mechanical forces in modulating cell fate decisions between survival and death, facilitating cell volume dynamics and maintaining germline homeostasis during oogenesis.

生殖细胞被组织成合胞体结构，其中单个细胞通过细胞间桥保持连接。在这种被称为生殖系囊肿的结构框架中，一部分生殖细胞扩大并发育成卵母细胞，而其他生殖细胞则缩小并因细胞死亡而消失。最近对秀丽隐杆线虫的研究表明，凋亡介导的生殖细胞死亡和存活生殖细胞的扩大都受机械力的调节。生殖细胞表现出由肌动球蛋白收缩性驱动的体积随机波动。由于囊肿内流体静压差异驱动的机械不稳定性，这种初始大小的异质性逐渐扩大，使较小的细胞倾向于收缩和随后的凋亡死亡。RAS/MAPK信号级联和ECT-2/RhoA通路进一步加强了这种机械不稳定性，两者都增强了肌动球蛋白的收缩性。存活的生殖细胞通过肌动球蛋白收缩介导的囊内流体动力流动获取细胞质物质，继续生长。总的来说，这些发现强调了机械力在调节细胞生存和死亡之间的命运决定、促进细胞体积动力学和维持卵子发生期间种系稳态方面的关键作用。

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引用次数: 0

Engineering the ovarian niche: Environmental control of folliculogenesis in vitro 工程卵巢生态位：体外卵泡发生的环境控制

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-20 DOI: 10.1016/j.semcdb.2025.103639

Arezoo Dadashzadeh , Saeid Moghassemi , Saba Nikanfar , Ellen C.R. Leonel , Shunran Zhang , Maria João Sousa , Thalles Fernando Rocha Ruiz , Christiani A. Amorim

Advancements in cancer therapies have significantly improved patient survival, but gonadotoxic treatments often compromise fertility, particularly in female patients. While ovarian tissue cryopreservation and transplantation are well-established fertility preservation options, they are not recommended for patients with blood-borne cancers or highly metastatic malignancies due to the risk of ovarian involvement. In these cases, follicle in vitro culture offers a promising alternative. However, folliculogenesis is a complex process that requires meticulous environmental control to mimic the ovarian niche. Key factors include biochemical signals delivered through culture media, biophysical support provided by three-dimensional biomaterials or the native extracellular matrix, and crucial cellular interactions that drive follicular development. Recent advances in biomaterial design have led to the creation of scaffolds that not only preserve structural integrity but also facilitate nutrient exchange and cell communication. Moreover, dynamic culture systems have shown superior outcomes compared to static models, offering a more physiologically relevant environment. This review explores the interplay of biochemical, biophysical, and mechanical factors in in vitro folliculogenesis. By synthesizing current innovations in scaffold design, culture systems, and bioactive supplementation, we outline key strategies for optimizing in vitro follicular development. These advances pave the way toward safer and more effective fertility preservation approaches for patients at high risk of ovarian metastasis and offer broader insights into reproductive biology and regenerative medicine. However, to fully realize this potential, further standardization, long-term safety studies, and critical evaluation of emerging technologies remain essential to enable robust clinical translation and personalized reproductive applications.

癌症治疗的进步显著提高了患者的生存率，但促性腺毒素治疗往往会损害生育能力，尤其是女性患者。虽然卵巢组织冷冻保存和移植是公认的保存生育能力的选择，但由于卵巢受累的风险，不推荐用于血源性癌症或高度转移性恶性肿瘤患者。在这些情况下，卵泡体外培养提供了一个有希望的选择。然而，卵泡发生是一个复杂的过程，需要细致的环境控制来模拟卵巢生态位。关键因素包括通过培养基传递的生化信号，三维生物材料或天然细胞外基质提供的生物物理支持，以及驱动卵泡发育的关键细胞相互作用。生物材料设计的最新进展导致支架的创造，不仅保持结构完整性，而且促进营养交换和细胞通讯。此外，与静态模型相比，动态培养系统显示出更好的结果，提供了一个更生理相关的环境。本文综述了体外卵泡形成过程中生物化学、生物物理和机械因素的相互作用。通过综合目前支架设计、培养系统和生物活性补充方面的创新，我们概述了优化体外卵泡发育的关键策略。这些进展为卵巢转移高风险患者提供更安全、更有效的生育保护方法铺平了道路，并为生殖生物学和再生医学提供了更广泛的见解。然而，为了充分发挥这一潜力，进一步的标准化、长期安全性研究和对新兴技术的批判性评估仍然是实现稳健的临床转化和个性化生殖应用的必要条件。

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引用次数: 0

The mechanics of shaping organs in plants 植物器官形成的机制

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-11 DOI: 10.1016/j.semcdb.2025.103640

Ankita Dash , Mabel Maria Mathew , Kalika Prasad

Mechanical forces are instrumental to shaping lifeforms, influencing development from the subcellular scale to the organismal scale. Here, we explore how mechanical forces manifest themselves in plants, driving deformations such as tissue folding, buckling, undulating patterns, and edge curving. These deformations result from modulations in fundamental cellular processes such as cell division, cell expansion, cell wall mechanics, and cytoskeletal organization. Cytoskeletal structure like microtubules, actin filaments respond to mechanical cues by generating localized stress patterns that shape cell structure and function. Mechanical forces can also regulate gene expression and gate mechanosensitive channels to regulate ion fluxes, thereby integrating physical forces with biochemical properties. We draw parallels between plant and animal kingdoms to show how these two kingdoms utilize mechanochemical effects to drive growth and morphogenesis.

机械力是塑造生命形式的工具，影响着从亚细胞尺度到有机体尺度的发展。在这里，我们探索机械力如何在植物中表现出来，驱动组织折叠、屈曲、波动模式和边缘弯曲等变形。这些变形是由细胞分裂、细胞扩增、细胞壁力学和细胞骨架组织等基本细胞过程的调节引起的。细胞骨架结构如微管、肌动蛋白丝通过产生局部应力模式来响应机械信号，从而塑造细胞结构和功能。机械力还可以调节基因表达，开启机械敏感通道来调节离子通量，从而将物理力与生化特性结合起来。我们在植物和动物王国之间进行了类比，以说明这两个王国如何利用机械化学效应来驱动生长和形态发生。

引用次数: 0

Capturing ovarian dynamics through spatial profiling of the mechano-microenvironment 通过机械微环境的空间分析捕捉卵巢动力学

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-11 DOI: 10.1016/j.semcdb.2025.103642

Kosei Tomida , Huan Ting Ong , Jennifer L. Young , Chii Jou Chan

In recent years, tissue mechanics has been recognized not as a passive outcome of development but may function as upstream regulators to guide cellular functions such as proliferation, migration, and differentiation. In mammalian ovaries, cross-scale mechanical signals arising from tissue deformation, extracellular matrix architecture, and intrafollicular pressure dynamically evolve over the reproductive lifespan, contributing to a complex biomechanical landscape. Despite increasing recognition of their role in regulating follicle development, mechanical signals from ovarian microenvironment are still often considered separately from changes in gene expression and metabolic pathways. In addition, comprehensive mapping of the ovarian mechano-microenvironment remains lacking, in part due to challenges in assessing mechanical information in ovaries. Here we discuss how emerging biophysical techniques, including the latest advancement in various omics technologies, allow us to probe ovarian mechanics across multiple length scales. Such an integrated approach will provide new insights on how force transmission, matrix remodeling, and cellular signaling intersect within defined spatial niches to regulate ovarian dynamics, paving the way for future understanding of the mechanobiological basis of reproductive disorders.

近年来，组织力学已被认为不是发育的被动结果，而是可能作为上游调节因子指导细胞功能，如增殖、迁移和分化。在哺乳动物卵巢中，由组织变形、细胞外基质结构和卵泡内压力引起的跨尺度机械信号在生殖寿命期间动态演变，形成了复杂的生物力学景观。尽管越来越多的人认识到它们在调节卵泡发育中的作用，但卵巢微环境的机械信号仍然经常与基因表达和代谢途径的变化分开考虑。此外，卵巢力学微环境的综合制图仍然缺乏，部分原因是评估卵巢力学信息的挑战。在这里，我们讨论了新兴的生物物理技术，包括各种组学技术的最新进展，如何使我们能够跨越多个长度尺度探索卵巢力学。这种整合的方法将为力量传递、基质重塑和细胞信号传导如何在确定的空间壁龛内交叉调节卵巢动力学提供新的见解，为未来理解生殖疾病的机械生物学基础铺平道路。

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引用次数: 0

Evolvability in vertebrate segmentation 脊椎动物分割的可进化性

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-08-05 DOI: 10.1016/j.semcdb.2025.103630

James E. Hammond, Callum V. Bucklow, Berta Verd

The number of vertebrae in the axial skeleton of vertebrates is extremely diverse, and reflects adaptations to a diverse range of habitats and lifestyles. The capacity for heritable evolutionary change in the number of vertebrae — its evolvability — is underpinned by the process of somitogenesis, which determines the number of somites that form in the early embryo. However, despite the evolvability of somitogenesis having been crucial for the success of the vertebrates across evolutionary history, the developmental sources of evolvability in somitogenesis are still unknown. Here, we review the evolution of somitogenesis and vertebral number, and attempt to identify sources of evolvability within this important developmental process.

脊椎动物轴向骨骼中椎骨的数量非常多样化，反映了对各种栖息地和生活方式的适应。椎骨数量的可遗传进化变化能力——它的可进化性——是由体细胞发生过程支撑的，体细胞发生过程决定了早期胚胎中形成的体细胞的数量。然而，尽管在整个进化史上，体细胞发生的可进化性对脊椎动物的成功至关重要，但体细胞发生的可进化性的发育来源仍然未知。在这里，我们回顾了体细胞发生和椎体数目的进化，并试图在这一重要的发育过程中确定可进化性的来源。

引用次数: 0

Retinal photoreceptor cilia and ciliopathies: Molecular mechanisms and therapeutic strategies 视网膜光感受器纤毛和纤毛病：分子机制和治疗策略

IF 6 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-07-28 DOI: 10.1016/j.semcdb.2025.103635

Lin Li , Jun Zhou , Jie Ran

Photoreceptor outer segments are specialized sensory cilia that are filled with flattened membranous discs responsible for transducing light into neural signals. These cilia maintain a dynamic system in which daily shedding of outer segments at distal tips balances continuous membrane synthesis, ensuring photoreceptor homeostasis. Mutations in ciliary genes impair the biogenesis or shedding of outer segments, leading to retinal ciliopathies. Recent studies have elucidated molecular mechanisms governing photoreceptor ciliary formation, maintenance, and renewal. In this review, we summarize current understanding of the spatiotemporal regulation of photoreceptor ciliogenesis and disc renewal, structural adaptations enabling light detection and protein trafficking, and pathogenic pathways from defective ciliary transport to photoreceptor degeneration. We further discuss emerging therapeutic strategies targeting cilia, including gene therapy and pharmacological intervention, as well as the potential application of targeted protein degradation and retinal organoid technologies, aimed at restoring ciliary function and photoreceptor viability.

光感受器外节是专门的感觉纤毛，充满扁平的膜状圆盘，负责将光转导成神经信号。这些纤毛维持着一个动态系统，在这个系统中，远端尖端外段的日常脱落平衡了连续的膜合成，确保了光感受器的稳态。纤毛基因突变损害生物发生或脱落的外段，导致视网膜纤毛病。最近的研究已经阐明了光感受器纤毛形成、维持和更新的分子机制。在这篇综述中，我们总结了目前对光感受器纤毛发生和盘更新的时空调节，光检测和蛋白质运输的结构适应，以及从缺陷纤毛运输到光感受器变性的致病途径的理解。我们进一步讨论了针对纤毛的新兴治疗策略，包括基因治疗和药物干预，以及靶向蛋白降解和视网膜类器官技术的潜在应用，旨在恢复纤毛功能和光感受器的活力。

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引用次数: 0