Seminars in cell & developmental biology最新文献_第6页

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 : 2025-08-01 Epub 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

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 : 2025-08-01 Epub 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

Designing multicellular cardiac tissue engineering technologies for clinical translation 设计用于临床翻译的多细胞心脏组织工程技术

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-07-01 Epub Date: 2025-04-29 DOI: 10.1016/j.semcdb.2025.103612

Andrew R. Laskary , James E. Hudson , Enzo R. Porrello

Cardiovascular diseases remain the leading cause of death worldwide—claiming one-third of all deaths every year. Current two-dimensional in vitro cell culture systems and animal models cannot completely recapitulate the clinical complexity of these diseases in humans. Therefore, there is a dire need for higher fidelity biological systems capable of replicating these phenotypes to inform clinical outcomes and therapeutic development. Cardiac tissue engineering (CTE) strategies have emerged to fulfill this need by the design of in vitro three-dimensional myocardial tissue systems from human pluripotent stem cells. In this way, CTE systems serve as highly controllable human models for a variety of applications—including for physiological and pathological modeling, drug discovery and preclinical testing platforms, and even direct therapeutic interventions in the clinic. Although significant progress has been made in the development of these CTE technologies, critical challenges remain and necessary refinements are required to derive more advanced human heart tissue technologies. In this review, we distill three focus areas for the field to address: I) Generating cardiac muscle cell types and scalable manufacturing methods, II) Engineering tissue structure, function, and analyses, and III) Curating system design for specific application. In each of our focus areas, we emphasize the importance of designing CTE systems capable of mimicking the intricate intercellular connectivity of the human heart and discuss fundamental design considerations that subsequently arise. We conclude by highlighting cutting-edge applications that use CTE technologies for clinical modeling and the direct repair of damaged and diseased hearts.

心血管疾病仍然是全世界死亡的主要原因——每年占所有死亡人数的三分之一。目前的二维体外细胞培养系统和动物模型不能完全概括这些疾病在人类中的临床复杂性。因此，迫切需要能够复制这些表型的高保真度生物系统，以告知临床结果和治疗发展。心脏组织工程（CTE）策略的出现是为了满足这一需求，通过设计体外三维心肌组织系统，从人类多能干细胞。通过这种方式，CTE系统可以作为高度可控的人体模型，用于各种应用，包括生理和病理建模、药物发现和临床前测试平台，甚至是临床中的直接治疗干预。尽管这些CTE技术的发展取得了重大进展，但仍然存在重大挑战，需要进行必要的改进，以获得更先进的人类心脏组织技术。在这篇综述中，我们提炼出该领域需要解决的三个重点领域：1)生成心肌细胞类型和可扩展的制造方法，2)工程组织结构，功能和分析，以及3)为特定应用策划系统设计。在我们的每个重点领域，我们强调设计能够模仿人类心脏复杂的细胞间连接的CTE系统的重要性，并讨论随后出现的基本设计考虑因素。最后，我们强调了使用CTE技术进行临床建模和直接修复受损和病变心脏的前沿应用。

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引用次数: 0

Why cellular computations challenge our design principles 为什么细胞计算挑战我们的设计原则

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-07-01 Epub Date: 2025-04-30 DOI: 10.1016/j.semcdb.2025.103616

Lewis Grozinger , Bruno Cuevas-Zuviría , Ángel Goñi-Moreno

Biological systems inherently perform computations, inspiring synthetic biologists to engineer biological systems capable of executing predefined computational functions for diverse applications. Typically, this involves applying principles from the design of conventional silicon-based computers to create novel biological systems, such as genetic Boolean gates and circuits. However, the natural evolution of biological computation has not adhered to these principles, and this distinction warrants careful consideration. Here, we explore several concepts connecting computational theory, living cells, and computers, which may offer insights into the development of increasingly sophisticated biological computations. While conventional computers approach theoretical limits, solving nearly all problems that are computationally solvable, biological computers have the opportunity to outperform them in specific niches and problem domains. Crucially, biocomputation does not necessarily need to scale to rival or replicate the capabilities of electronic computation. Rather, efforts to re-engineer biology must recognise that life has evolved and optimised itself to solve specific problems using its own principles. Consequently, intelligently designed cellular computations will diverge from traditional computing in both implementation and application.

生物系统固有地执行计算，激励合成生物学家设计能够执行各种应用的预定义计算功能的生物系统。通常，这涉及到应用传统硅基计算机的设计原理来创建新的生物系统，如遗传布尔门和电路。然而，生物计算的自然进化并没有遵循这些原则，这种区别值得仔细考虑。在这里，我们探讨了连接计算理论、活细胞和计算机的几个概念，这些概念可能为日益复杂的生物计算的发展提供见解。当传统计算机接近理论极限，解决几乎所有可计算解决的问题时，生物计算机有机会在特定的利基和问题领域超越它们。至关重要的是，生物计算并不一定需要规模来竞争或复制电子计算的能力。相反，重新设计生物学的努力必须认识到，生命已经进化并优化了自己，以利用自己的原则解决特定的问题。因此，智能设计的蜂窝计算将在实现和应用上与传统计算产生分歧。

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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 : 2025-07-01 Epub 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

The role of granulosa cells in oocyte development and aging: Mechanisms and therapeutic opportunities 颗粒细胞在卵母细胞发育和衰老中的作用：机制和治疗机会

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-07-01 Epub Date: 2025-04-28 DOI: 10.1016/j.semcdb.2025.103614

HaiYang Wang

Granulosa cells (GCs) are essential for oocyte maturation, providing metabolic support, hormonal signaling, and structural integrity critical to successful follicular development. However, advancing age disrupts these functions, driven by factors such as increased oxidative stress, mitochondrial dysfunction, and transcriptomic and proteomic alterations. These age-related changes in GCs contribute to compromised oocyte quality, diminished follicular support, and a decline in fertility, particularly in women of advanced maternal age. This review highlights recent progress in understanding the pivotal roles of GCs in maintaining oocyte health, with a focus on the mechanisms underlying their aging-related dysfunction. Furthermore, we explore promising therapeutic strategies, including antioxidant therapies, metabolic modulators, and GC-based rejuvenation techniques, aimed at mitigating the impacts of reproductive aging. By consolidating and analyzing existing research, this review provides valuable perspectives on fertility preservation and factors shaping reproductive outcomes in women of advanced maternal age.

颗粒细胞（GCs）对卵母细胞成熟至关重要，提供代谢支持、激素信号和结构完整性，对卵泡的成功发育至关重要。然而，在氧化应激增加、线粒体功能障碍、转录组和蛋白质组改变等因素的驱动下，年龄的增长会破坏这些功能。这些与年龄相关的GCs变化导致卵母细胞质量受损，卵泡支持减少，生育能力下降，特别是高龄产妇。本文综述了近年来在理解GCs在维持卵母细胞健康中的关键作用方面的进展，并重点讨论了GCs衰老相关功能障碍的机制。此外，我们探索了有前景的治疗策略，包括抗氧化疗法、代谢调节剂和基于gc的年轻化技术，旨在减轻生殖衰老的影响。通过对现有研究的整合和分析，本综述为高龄产妇的生育能力保存和影响生育结果的因素提供了有价值的观点。

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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 : 2025-07-01 Epub 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 : 2025-07-01 Epub 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

Gossiping about death: Apoptosis-induced ERK waves as coordinators of multicellular fate decisions 关于死亡的八卦：凋亡诱导的ERK波作为多细胞命运决定的协调者

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-07-01 Epub Date: 2025-04-24 DOI: 10.1016/j.semcdb.2025.103615

Paolo Armando Gagliardi , Olivier Pertz

Apoptosis is now recognized as a highly dynamic process that involves the release of a large set of signaling molecules that convey information to cells neighboring an apoptotic site. Recent studies in epithelial systems have discovered that apoptotic cells trigger waves of pulses of mitogen-activated protein kinase (MAPK) / extracellular signal-regulated kinase (ERK) pathway activity in their neighbors. At the single-cell level, the ERK pulses emerge from the MAPK pathway's excitable network properties, such as ultrasensitivity and adaptation. At the cell population level, apoptosis-induced ERK waves (AiEWs) emerge from propagation of ERK pulses across cells via a mechanism that involves mechanical inputs and paracrine signaling. AiEWs enable cell populations to dynamically coordinate fate decision signaling during tissue homeostasis and development. This spatio-temporal signaling mechanism can be hijacked by cancer cells to induce drug-tolerant persister states when apoptosis is triggered by cytotoxic or targeted therapies, undermining treatment efficacy. In this review, we summarize our current understanding of AiEWs, including their initiation, propagation, and coordination of fate decision signaling within a population. We discuss how the relatively simple properties of single cells, and their interactions within a collective coordinate these dynamic signaling patterns. We highlight their implication in resistance to cancer therapy and explore potential strategies to target these waves to re-sensitize cancer cells. Finally, we discuss emerging technologies and future directions to expand the study of this biological phenomenon.

细胞凋亡现在被认为是一个高度动态的过程，涉及释放大量信号分子，将信息传递给凋亡位点附近的细胞。最近对上皮系统的研究发现，凋亡细胞在其邻近细胞中触发有丝分裂原激活蛋白激酶(MAPK) /细胞外信号调节激酶（ERK）通路活性的脉冲波。在单细胞水平上，ERK脉冲来自MAPK通路的可兴奋网络特性，如超灵敏度和适应性。在细胞群水平上，凋亡诱导的ERK波（AiEWs）是由ERK脉冲在细胞间传播产生的，其机制涉及机械输入和旁分泌信号。AiEWs使细胞群在组织稳态和发育过程中动态协调命运决定信号。当细胞毒性或靶向治疗引发细胞凋亡时，这种时空信号机制可被癌细胞劫持，诱导耐药持续状态，从而破坏治疗效果。在这篇综述中，我们总结了我们目前对AiEWs的理解，包括它们的起源、传播和种群内命运决定信号的协调。我们讨论了单个细胞的相对简单的特性，以及它们在一个集体中的相互作用如何协调这些动态信号模式。我们强调了它们在癌症治疗耐药中的意义，并探索了靶向这些波使癌细胞重新敏感的潜在策略。最后，我们讨论了新兴技术和未来的发展方向，以扩大这一生物现象的研究。

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引用次数: 0

Immune-mediated cardiac development and regeneration 免疫介导的心脏发育和再生

IF 6.2 2区生物学 Q1 CELL BIOLOGY

Seminars in cell & developmental biology

Pub Date : 2025-07-01 Epub Date: 2025-05-01 DOI: 10.1016/j.semcdb.2025.103613

Timothy C. Byatt , Ehsan Razaghi , Selin Tüzüner , Filipa C. Simões

The complex interplay between the immune and cardiovascular systems during development, homeostasis and regeneration represents a rapidly evolving field in cardiac biology. Single cell technologies, spatial mapping and computational analysis have revolutionised our understanding of the diversity and functional specialisation of immune cells within the heart. From the earliest stages of cardiogenesis, where primitive macrophages guide heart tube formation, to the complex choreography of inflammation and its resolution during regeneration, immune cells emerge as central orchestrators of cardiac fate. Translating these fundamental insights into clinical applications represents a major challenge and opportunity for the field. In this Review, we decode the immunological blueprint of heart development and regeneration to transform cardiovascular disease treatment and unlock the regenerative capacity of the human heart.

免疫系统和心血管系统在发育、体内平衡和再生过程中的复杂相互作用是心脏生物学中一个快速发展的领域。单细胞技术、空间制图和计算分析彻底改变了我们对心脏内免疫细胞多样性和功能专门化的理解。从心脏发生的最初阶段，原始巨噬细胞引导心管的形成，到炎症的复杂编排及其在再生过程中的消退，免疫细胞成为心脏命运的中心策划者。将这些基本见解转化为临床应用是该领域的重大挑战和机遇。在这篇综述中，我们解码心脏发育和再生的免疫蓝图，以改变心血管疾病的治疗，并解锁人类心脏的再生能力。

引用次数: 0