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Sir John Gurdon and the rise of molecular developmental biology 约翰·戈登爵士和分子发育生物学的兴起
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-10-31 DOI: 10.1016/j.cdev.2025.204056
Edward M. De Robertis
John B. Gurdon was one of the most beloved developmental biologists of our times, who enjoyed a long life completely immersed in science. Blessed with a very important discovery at age 25, he used his distinguished position for the common good of other biologists. John's life epitomizes the Golden Rule of Western Civilization – love your neighbor as yourself – to the great benefit of his field. As a graduate student, he demonstrated that somatic cells retained the complete gene repertoire to differentiate into all cell types. He developed the Xenopus oocyte as a living test tube for molecular biology. His microinjection studies provided the first vertebrate system to translate mRNA, transcribe DNA, and express cloned genes. He investigated the reprogramming of somatic nuclei to the gene expression pattern of oocytes for many decades. His discoveries were foundational to the use of stem cells for tissue therapies and were recognized with the 2012 Nobel prize for Medicine. He was responsible, more than any other person, for introducing Xenopus as a research organism for molecular biology. He was a wonderful mentor who taught by example and built new research institutes. His tireless support for scientific societies organized by scientists independently of governments led him to deliver incomparable lectures throughout the world, inspiring generations of developmental biologists. His secret weapon was to never stop working at the bench with his beloved oocytes and embryos. Above all, he was a good man. Sir John passed away peacefully at home, surrounded by his family at age 92.
约翰·b·戈登是我们这个时代最受爱戴的发育生物学家之一,他一生都沉浸在科学中。25岁时,他有幸有了一项非常重要的发现,他利用自己的杰出地位为其他生物学家谋福利。约翰的一生体现了西方文明的黄金法则——爱邻如己——为他的领域带来了巨大的利益。作为一名研究生,他证明了体细胞保留了完整的基因库,可以分化成所有的细胞类型。他研制出非洲爪蟾卵母细胞,作为分子生物学的活试管。他的显微注射研究提供了第一个翻译mRNA、转录DNA和表达克隆基因的脊椎动物系统。几十年来,他一直在研究体细胞核对卵母细胞基因表达模式的重编程。他的发现为干细胞用于组织治疗奠定了基础,并获得了2012年诺贝尔医学奖。他比任何人都更有责任把非洲爪蟾作为分子生物学的研究对象。他是一位出色的导师,他以身作则,建立了新的研究机构。他对独立于政府的科学家组织的科学协会孜孜不倦的支持,使他在世界各地发表了无与伦比的演讲,激励了一代又一代的发育生物学家。他的秘密武器是永远不会停止与他心爱的卵母细胞和胚胎一起工作。最重要的是,他是个好人。约翰爵士在家中平静地去世,享年92岁,家人在他的陪伴下。
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引用次数: 0
Small molecules induces dorsal root ganglion satellite glial cells to differentiate into sensory neuron-like cells 小分子诱导背根神经节卫星胶质细胞向感觉神经元样细胞分化。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2026-02-12 DOI: 10.1016/j.cdev.2026.204073
Xiaohua Weng , Jinwei Yang , Wei Ma , Liyan Li
The inability of damaged neurons to regenerate poses a significant challenge in the repair of peripheral nerve injuries. Exogenous cell therapies, such as those involving neural stem cells or induced pluripotent stem cells, are limited by immune rejection and ethical concerns. Somatic cells offer a promising alternative, as they can be reprogrammed and differentiated into neuron-like cells, thereby promoting nerve repair. Satellite glial cells (SGCs) within the dorsal root ganglion (DRG) have the capacity to differentiate into multiple cell types. In this study, chemical small molecules were used to replace transcription factors and induce DRG-derived SGCs to differentiate into sensory neuron-like cells. Subsequently, cell viability, morphology, and functionality were evaluated using CCK-8 assays, immunocytochemistry, qRT-PCR, ELISA, confocal calcium imaging, and ultra-high-resolution transmission electron microscopy. The induced cells expressed key sensory neuron markers, including CGRP, PSD95, Synapsin, PRPH, TrkA, TrkB, TrkC, Ret, AnkyrinG, and Brn3a. Moreover, they displayed gene expression patterns associated with sensory neuron development, such as those of Avil, TrkA, Brn3a, Isl1, Runx3, and Shox2. Importantly, these cells exhibited calcium transients in response to KCl, BayK, and capsaicin stimulation. Capsaicin treatment also resulted in increased levels of CGRP and substance P, suggesting that the induced cells exhibit characteristics of mature neurons, including synaptic structures, functional calcium channels, and active signaling pathways. Our findings demonstrate that DRG-derived SGCs can be chemically induced to differentiate into sensory neuron-like cells, representing a novel approach for neuronal cell fate acquisition and a potential cell source for peripheral nerve repair.
受损神经元不能再生是周围神经损伤修复的一大难题。外源性细胞疗法,例如涉及神经干细胞或诱导多能干细胞的疗法,受到免疫排斥和伦理问题的限制。体细胞提供了一个很有前途的选择,因为它们可以被重新编程并分化成神经元样细胞,从而促进神经修复。背根神经节(DRG)内的卫星胶质细胞(SGCs)具有向多种细胞类型分化的能力。本研究利用化学小分子替代转录因子,诱导drg源性SGCs向感觉神经元样细胞分化。随后,使用CCK-8测定、免疫细胞化学、qRT-PCR、ELISA、共聚焦钙成像和超高分辨率透射电子显微镜评估细胞活力、形态和功能。诱导细胞表达关键感觉神经元标志物,包括CGRP、PSD95、Synapsin、PRPH、TrkA、TrkB、TrkC、Ret、AnkyrinG和Brn3a。此外,它们还显示了与感觉神经元发育相关的基因表达模式,如Avil、TrkA、Brn3a、Isl1、Runx3和Shox2。重要的是,这些细胞在KCl、BayK和辣椒素刺激下表现出钙瞬变。辣椒素处理也导致CGRP和P物质水平升高,表明诱导细胞表现出成熟神经元的特征,包括突触结构、功能钙通道和活跃的信号通路。我们的研究结果表明,drg衍生的SGCs可以被化学诱导分化为感觉神经元样细胞,这代表了神经元细胞命运获取的新途径和周围神经修复的潜在细胞来源。
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引用次数: 0
Transient versican expression is required for β1-integrin accumulation during podocyte layer morphogenesis in amphibian developing kidney 在两栖动物肾脏发育过程中足细胞层形态发生过程中β1-整合素的积累需要瞬时型表达。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-12-13 DOI: 10.1016/j.cdev.2025.204062
Isabelle Buisson , Jean-François Riou , Muriel Umbhauer , Ronan Le Bouffant , Valérie Bello
The functional organization of the vertebrate nephron is remarkably conserved, yet the morphogenetic processes underlying nephrogenesis vary across species and kidney types. The Xenopus larval kidney, the pronephros, is a non-integrated nephron where plasma filtrates are first released into a coelomic compartment, the nephrocoel, before entering the tubular compartment through ciliated nephrostomes. Mechanisms of pronephros morphogenesis, especially the role of the extracellular matrix (ECM), remain poorly understood. This study investigates the function of the ECM component versican (vcan) in the development of the pronephric kidney in X. laevis, focusing on non-integrated nephron features: the glomus, nephrocoel, and nephrostomes. Vcan is dynamically expressed in the ECM surrounding the developing tubule and the podocyte layer of the glomus, with transient presence in the differentiating podocyte region prior to the formation of the concave podocyte pocket that accumulates β1-integrin. Morpholino-mediated vcan depletion leads to fusion of proximal tubule branches, tubular dilation, and loss of proximal convolutions, without affecting nephrostomes. Glomus morphogenesis is severely disrupted, the podocyte layer fails to form its characteristic C-shaped structure, and β1-integrin fails to accumulate, although the podocyte differentiation marker nphs2 remains expressed. Other ECM components, including fibrillin, laminin, and fibronectin, remain correctly localized, indicating that the phenotype is not due to general ECM disorganization. Together, these findings identify a specific and temporally regulated role for vcan in glomus morphogenesis, likely by enabling β1-integrin accumulation and promoting cell–ECM interactions essential for proper podocyte layer assembly, thereby refining our understanding of ECM dynamics in kidney development.
脊椎动物肾元的功能组织是非常保守的,然而肾形成的形态发生过程在不同物种和肾类型之间是不同的。爪蟾幼体肾脏(原肾)是一个非整合肾元,血浆滤液首先被释放到体腔室(肾腔),然后通过纤毛肾造口进入肾小管室。原肾形态发生的机制,特别是细胞外基质(ECM)的作用,仍然知之甚少。本研究探讨了ECM组分versican (vcan)在肾小球肾小球形成中的功能,重点关注非整合肾元特征:肾小球、肾结和肾造口。Vcan在发育中的小管和足细胞层周围的ECM中动态表达,在形成凹形足细胞袋积聚β1-整合素之前,在分化的足细胞区短暂存在。morpholinos介导的vcan耗竭导致近端小管分支融合、小管扩张和近端曲丢失,而不影响肾造口。尽管足细胞分化标记物nphs2仍有表达,但球囊形态发生严重破坏,足细胞层不能形成其特有的c形结构,β1-整合素不能积累。其他ECM成分,包括原纤维蛋白,层粘连蛋白和纤维连接蛋白,仍然正确定位,表明表型不是由于一般的ECM紊乱。总之,这些发现确定了vcan在肾小球形态发生中的特定和暂时调节作用,可能是通过促进β1-整合素积累和促进细胞-ECM相互作用,这是足细胞层适当组装所必需的,从而完善了我们对肾脏发育中ECM动力学的理解。
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引用次数: 0
Tissue-resident macrophages contribute to ear hole regeneration of early postnatal mice 组织常驻巨噬细胞促进早期产后小鼠耳孔再生。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-10-28 DOI: 10.1016/j.cdev.2025.204055
René Fernando Abarca-Buis , Blanca Alicia Barredo-Prieto , David Garciadiego-Cázares , María Elena Contreras-Figueroa , Edgar Krötzsch
Healing of ear holes made in early postnatal mice represents an accessible model for the study of the regeneration of multiple tissues in mammals. This regenerative process involves three phases: wound healing, blastema formation, and re-differentiation. Classical models for regeneration studies have implicated macrophages as key cells for regeneration progression. In this study macrophage distribution and macrophage depletion experiments were conducted to evaluate whether these cells have a role during ear hole regeneration in early postnatal mice. Using the pan-macrophage markers CD68 and F4/80, we discriminate infiltrating from tissue-resident macrophages. In addition to expressing F4/80, tissue-resident macrophages also showed the presence of iNOS, a marker of pro-inflammatory macrophages. Unexpectedly, depletion of macrophages by clodronate liposomes administration during the wound healing stage of ear hole regeneration of early postnatal-age mice resulted in an increased number of infiltrating CD68+ cells and a deletion of F4/80+ macrophages with the subsequent delay in re-epithelialization and blastema formation. Under this experimental condition, IL10 was not affected during the wound healing phase, but its levels decreased when the re-population of F4/80+ tissue-resident macrophages was evident in the regenerating tissues. In addition, the administration of clodronate liposomes during the re-differentiation stage accelerated the maturation of regenerating elastic cartilage. These results indicate that F4/80+ tissue-resident macrophages control the infiltration of determined immune cells and are the main macrophage subpopulation that contributes to the regeneration of ear holes made in early postnatal mice.
早期产后小鼠耳孔愈合为哺乳动物多组织再生研究提供了一种可行的模型。这种再生过程包括三个阶段:伤口愈合、胚基形成和再分化。再生研究的经典模型表明巨噬细胞是再生进展的关键细胞。本研究通过巨噬细胞分布和巨噬细胞消耗实验来评估这些细胞是否在早期出生后小鼠耳孔再生中起作用。利用泛巨噬细胞标志物CD68和F4/80,我们区分浸润性和组织内巨噬细胞。除了表达F4/80外,组织内巨噬细胞还存在促炎巨噬细胞的标志物iNOS。出乎意料的是,在出生后早期小鼠耳孔再生的伤口愈合阶段,氯钠脂质体使巨噬细胞消耗,导致CD68+浸润细胞数量增加,F4/80+巨噬细胞缺失,随后再上皮化和囊胚形成延迟。在本实验条件下,il - 10在伤口愈合阶段不受影响,但当F4/80+组织巨噬细胞在再生组织中明显重新聚集时,其水平下降。此外,在再分化阶段给予氯膦酸脂质体加速了再生弹性软骨的成熟。这些结果表明,F4/80+组织内巨噬细胞控制着确定的免疫细胞的浸润,是促进出生后早期小鼠耳孔再生的主要巨噬细胞亚群。
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引用次数: 0
Sialoglycoproteins and sialyltransferases: Key regulators of blastocyst formation 唾液糖蛋白和唾液转移酶:囊胚形成的关键调节因子。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-11-20 DOI: 10.1016/j.cdev.2025.204057
Pélagie Douchez , Ingrid Fliniaux , Yoshiko Takeda-Uchimura , Matthieu Marin , Alain Martoriati , Anne Harduin-Lepers , Katia Cailliau
Following fertilization, there is an initial period of rapid cell division that leads to the formation of a multicellular structure known as the blastula, or blastocyst. Within this structure, sialic acids play a key role in influencing cellular processes such as signaling, cell-to-cell contact, and adhesion. In species that develop internally, the blastocyst undergoes implantation and placentation, which depend on maternal immunomodulation facilitated by sialylated proteins and enzymes involved in the biosynthesis of sialic acids. Although research has shown that the elimination of certain initial enzymes in the sialic acid synthetic pathway can lead to reduced embryonic viability, the precise role of these enzymes remains to be further investigated, particularly in the blastula of externally developing species, which have received limited attention. Recently developed blastoid models present promising prospects for future research in this field.
受精后,有一个细胞快速分裂的初始阶段,导致形成一个多细胞结构,称为囊胚或囊胚。在这个结构中,唾液酸在影响细胞过程中发挥关键作用,如信号传导、细胞间接触和粘附。在内部发育的物种中,囊胚经历着床和胎盘,这依赖于母体免疫调节,由唾液酸生物合成的唾液化蛋白和酶促进。虽然有研究表明,唾液酸合成途径中某些初始酶的消除会导致胚胎活力降低,但这些酶的确切作用仍有待进一步研究,特别是在外部发育物种的囊胚中,这方面的研究有限。近年来发展的囊胚模型为该领域的研究提供了良好的前景。
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引用次数: 0
Signalling molecules and microenvironment modulation in skin regeneration of chronic wound repair: A cellular perspective 信号分子和微环境调节在皮肤再生的慢性伤口修复:一个细胞的观点。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-09-30 DOI: 10.1016/j.cdev.2025.204053
Keren Celestina Mendonce , Naveen Palani , P. Monisha , Parthasarathy Surya , Suriyaprakash Rajadesingu
Tissue repair is an intricate biological process involving cellular and molecular mechanisms. These mechanisms coordinate the repair of damaged tissue, relying on the function of several signalling molecules. Growth factors, cytokines, and hormones perform a fundamental role in tissue regeneration, especially in skin regeneration. On the other hand, in case of diabetes or chronic wounds, the synthesis and regulation of these signalling molecules may be disrupted. Despite advances in medical science, chronic, non-healing wounds remain a continuous challenge, often characterized by reduced angiogenesis, impaired epithelialization, irregular granulation tissue formation, and elevated inflammation. This highlights the need to explore their therapeutic applications and the possibility of external production or stimulation for improved healing. The cellular intricacies are revealed within the wounded environment, explaining the functions of each signalling molecule, thus providing a roadmap for therapeutic exploration. It scrutinizes the complexities of venous and arterial ulcers, diabetic wounds, and complex burn wounds, which indicates the urgency of coming up with innovative interventions. From the modulation of wound microenvironments will arise new treatment modalities that spur tissue restoration with efficacy. Scientists have explored the wound healing properties of Vascular Endothelial Growth Factor, Platelet Derived Growth Factor, Transforming Growth Factor-β, granulocyte-macrophage colony-stimulating factor, estradiol benzoate, thyroxine, and erythropoietin. This review article acts as a guide for better treatments that can improve wound healing.
组织修复是一个复杂的生物学过程,涉及细胞和分子机制。这些机制依赖于几个信号分子的功能来协调受损组织的修复。生长因子、细胞因子和激素在组织再生,尤其是皮肤再生中起着重要作用。另一方面,在糖尿病或慢性创伤的情况下,这些信号分子的合成和调节可能会被破坏。尽管医学科学取得了进步,但慢性、不愈合的伤口仍然是一个持续的挑战,通常以血管生成减少、上皮化受损、不规则肉芽组织形成和炎症升高为特征。这突出了探索其治疗应用和外部生产或刺激改善愈合的可能性的必要性。在受伤的环境中揭示了细胞的复杂性,解释了每个信号分子的功能,从而为治疗探索提供了路线图。它仔细研究了静脉和动脉溃疡、糖尿病伤口和复杂烧伤伤口的复杂性,这表明提出创新干预措施的紧迫性。从伤口微环境的调节将产生新的治疗方式,刺激组织恢复与有效。科学家们探索了血管内皮生长因子、血小板衍生生长因子、转化生长因子-β、粒细胞-巨噬细胞集落刺激因子、苯甲酸雌二醇、甲状腺素和促红细胞生成素的伤口愈合特性。这篇综述文章作为指导更好的治疗可以提高伤口愈合。
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引用次数: 0
A novel role of Mef2a in mitochondrial homeostasis and muscle regeneration during sarcopenia Mef2a在肌肉减少症期间线粒体稳态和肌肉再生中的新作用。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-12-11 DOI: 10.1016/j.cdev.2025.204063
Xin Tao , Suhong Zhang , Yue Li, Gongbing Tu, Dianfu Zhang, Liping Yin
Sarcopenia, characterized by an age-related decline in skeletal muscle mass and function, is closely associated with mitochondrial dysfunction. This study aimed to explore the role of myocyte enhancer factor 2A (MEF2A) in alleviating sarcopenia, focusing on its regulatory effect on mitochondrial homeostasis. AAV9-MEF2A was administered to 24-month-old male SAMP8 mice, and their endurance capacity and muscle histology were assessed. In vitro, MEF2A was overexpressed in C2C12 cells to examine its impact on myoblast proliferation and differentiation. Chromatin immunoprecipitation (ChIP), luciferase assays, and rescue experiments were conducted to identify downstream targets and validate the MEF2A-regulated signaling pathway. MEF2A overexpression significantly enhanced endurance performance, with a 1.17-fold increase in muscle mass, a 2.4 to 4.9-fold decrease in muscle atrophy markers compared to the AAV9-NC group, and a nearly 2 to 3-fold increase in mitochondrial biogenesis and antioxidant enzyme expression in aged mice. In C2C12 cells, MEF2A stimulated proliferation (1.8 fold increase in EdU-positive cells vs vector group) and differentiation (2 to 3-fold increase in differentiation markers vs vector group) while improving mitochondrial function through 1.5 to 2-fold increases in both OxPhos complex proteins and mitochondrial biogenesis genes compared to vector control. Mechanistically, MEF2A directly activated the PGC-1α/NRF2 axis, as validated by ChIP and reporter assays. Rescue experiments further verified the critical role of this pathway in MEF2A-mediated effects. These findings demonstrate that MEF2A mitigates sarcopenia by improving mitochondrial function and promoting muscle regeneration via activation of the PGC-1α/NRF2 signaling axis. MEF2A represents a promising therapeutic target for combating age-related muscle degeneration.
骨骼肌减少症的特征是骨骼肌质量和功能与年龄相关的下降,与线粒体功能障碍密切相关。本研究旨在探讨肌细胞增强因子2A (myocyte enhancer factor 2A, MEF2A)在缓解肌少症中的作用,重点关注其对线粒体稳态的调节作用。给予24月龄雄性SAMP8小鼠AAV9-MEF2A,评估其耐力和肌肉组织学。体外,MEF2A在C2C12细胞中过表达,检测其对成肌细胞增殖和分化的影响。通过染色质免疫沉淀(ChIP)、荧光素酶测定和救援实验来确定下游靶点并验证mef2a调节的信号通路。MEF2A过表达显著提高了耐力表现,与AAV9-NC组相比,老年小鼠肌肉质量增加1.17倍,肌肉萎缩标志物减少2.4 - 4.9倍,线粒体生物发生和抗氧化酶表达增加近2 - 3倍。在C2C12细胞中,MEF2A刺激了增殖(edu阳性细胞比载体组增加1.8倍)和分化(分化标记物比载体组增加2至3倍),同时通过OxPhos复合物蛋白和线粒体生物发生基因比载体对照增加1.5至2倍来改善线粒体功能。在机制上,MEF2A直接激活了PGC-1α/NRF2轴,通过ChIP和报告基因实验证实了这一点。救援实验进一步验证了该通路在mef2a介导作用中的关键作用。这些发现表明,MEF2A通过激活PGC-1α/NRF2信号轴,改善线粒体功能和促进肌肉再生,从而减轻肌肉减少症。MEF2A代表了对抗年龄相关性肌肉变性的一个有希望的治疗靶点。
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引用次数: 0
Physiological effect of cytokines on adult neurogenesis: a focus on in vivo knock-out studies 细胞因子对成人神经发生的生理作用:体内敲除研究的焦点。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2026-02-03 DOI: 10.1016/j.cdev.2026.204072
Narjess Haidar , Laure Salvon, Amnah Al-Sayyar, Oussama Kassem, Audrey Romano, Rejane Rua
Cytokines, central mediators of immune signaling, have emerged as pivotal regulators of neural stem cell (NSC) biology. Once regarded as immune-privileged, the central nervous system is now recognized as a dynamic site of immune-neural interaction, where meningeal and parenchymal immune cells modulate neurogenesis and brain plasticity through cytokine release. This review synthesizes current quantitative evidence on the effects of key cytokines including IL-6, FGF2, IL-15, IL-22, IL-10, and TNF-α on mouse NSCs studied exclusively in knockout models in vivo. This approach allows for a clearer understanding of their physiological roles, minimizing artefacts associated with in vitro systems, overexpression models, or inflammatory contexts, and focusing instead on their homeostatic functions. Collectively, these studies demonstrate that cytokine signaling profoundly influences NSC fate, proliferation, and differentiation. Importantly, by mapping cytokine expression within the dentate gyrus, the subventricular zone neurogenic niches, and the meninges, we put forward the provocative idea that brain borders are major sources of these factors, rather than the dentate gyrus itself. Understanding how immune-derived cues shape the NSC niche is critical for uncovering mechanisms underlying brain function, plasticity, and repair, with potential implications for neurodevelopmental, neuropsychiatric, and neurodegenerative disorders.
细胞因子是免疫信号的中枢介质,已成为神经干细胞生物学的关键调节因子。中枢神经系统曾经被认为是免疫特权,现在被认为是免疫-神经相互作用的动态部位,脑膜和实质免疫细胞通过细胞因子的释放调节神经发生和大脑可塑性。本文综合了目前在小鼠体内敲除模型中研究的关键细胞因子包括IL-6、FGF2、IL-15、IL-22、IL-10和TNF-α对小鼠NSCs影响的定量证据。这种方法可以更清楚地了解它们的生理作用,最大限度地减少与体外系统、过表达模型或炎症背景相关的人工产物,并将重点放在它们的稳态功能上。总的来说,这些研究表明细胞因子信号深刻地影响NSC的命运、增殖和分化。重要的是,通过绘制齿状回、脑室下区神经源性壁龛和脑膜内的细胞因子表达图谱,我们提出了一个具有挑战性的观点,即脑边界是这些因素的主要来源,而不是齿状回本身。了解免疫来源线索如何塑造NSC生态位对于揭示脑功能、可塑性和修复的潜在机制至关重要,对神经发育、神经精神和神经退行性疾病具有潜在意义。
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引用次数: 0
Extracellular vesicles: A complex array of particles involved in cell-to-cell communication for tissue homeostasis 细胞外囊泡:一种复杂的粒子阵列,参与组织内稳态的细胞间通讯。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-10-24 DOI: 10.1016/j.cdev.2025.204054
Natayme Rocha Tartaglia , Lorena Martin-Jaular , Alain Joliot , Clotilde Théry
Communication between cells is an inescapable feature of every multicellular organism, from the coordination of development during embryogenesis to the maintenance of homeostasis throughout adulthood. Extracellular vesicles (EVs) are new and central players in intercellular communication processes, by carrying multiple signals at once and acting in concert with well-described soluble effectors released in the environment. These membrane-enclosed particles are released by all cells in their environment. Their lipid bilayer protects their internal content while exposing surface determinants, allowing EVs to interact with target cells and/or surrounding extracellular matrix. EVs can also escape to blood or lymph circulation and reach further away organs. By carrying multiple signals, locally or at a distance, EVs are increasingly considered as players in the coordination of physiological processes within and across tissues. Here, we briefly summarize the many studies describing physiological functions of EVs, and discuss their actual demonstration in vivo. In addition, we discuss this knowledge in light of our current understanding on the heterogeneity of EVs, the complex composition of EV-containing preparations and the consequences to unravel the specific activities of EVs, including subtypes of EVs such as exosomes, and of other extracellular particles (EPs).
细胞间的交流是每一个多细胞生物不可避免的特征,从胚胎发育的协调到整个成年期的体内平衡的维持。细胞外囊泡(EVs)是细胞间通讯过程中新的核心角色,它同时携带多种信号,并与环境中释放的可溶性效应物协同作用。这些被膜包裹的颗粒被周围环境中的所有细胞释放出来。它们的脂质双分子层在暴露表面决定因素的同时保护其内部内容,允许ev与靶细胞和/或周围的细胞外基质相互作用。电动汽车也可以逃逸到血液或淋巴循环,到达更远的器官。通过在局部或远处携带多种信号,电动汽车越来越多地被认为是组织内和组织间生理过程协调的参与者。在此,我们简要总结了许多描述电动汽车生理功能的研究,并讨论了它们在体内的实际证明。此外,根据我们目前对ev异质性的理解,我们讨论了这些知识,含ev制剂的复杂组成以及揭示ev的特定活性的后果,包括ev的亚型,如外泌体和其他细胞外颗粒(EPs)。
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引用次数: 0
LSM14A, an LSM family protein, is dispensable for spermatogenesis and male fertility in mice LSM14A是LSM家族的一种蛋白,在小鼠的精子发生和雄性生育中是必不可少的。
IF 2 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-11-12 DOI: 10.1016/j.cdev.2025.204058
Xu Fan, Ling Yang, Xiao Wang, Nana Li, Zhengpin Wang
The LSM (Like-Smith) family comprises RNA-binding proteins (RBPs) that are key regulators of RNA metabolism. LSM14A, a member of this family (designated Lsm14a in mice), participates in RNA processing within cytoplasmic processing bodies (P-bodies). The mouse Lsm14a gene is localized to chromosome 7qB1, spans 48.67 kilobases (kb), and encodes a 462-amino-acid protein that exhibits 94.53 % amino acid identity with human LSM14A. However, the expression profile of LSM14A in male reproductive organs and its functional relevance to male fertility remain uncharacterized. In this study, we report that LSM14A is expressed in the mouse testis and localizes to the cytoplasm of germ cells, from spermatogonia to elongating spermatids. To investigate LSM14A function, we generated germ cell-specific Lsm14a conditional knockout (cKO) mice. Lsm14a cKO male mice displayed normal growth, development, and fertility. Histological examination of Lsm14a cKO testes revealed preserved spermatogenesis and seminiferous tubule structure. Lsm14a cKO sperm exhibited normal morphology, acrosome integrity, and motility. The loss of Lsm14a in the testes did not significantly affect P-body formation, suggesting that genetic compensation by other LSM family members may have been activated upon Lsm14a knockout, thereby compensating for its loss of function. Collectively, these findings demonstrate that LSM14A is dispensable for spermatogenesis and male fertility in mice.
LSM (Like-Smith)家族由RNA结合蛋白(rbp)组成,rbp是RNA代谢的关键调节因子。LSM14A是该家族的一员(在小鼠中命名为LSM14A),参与细胞质加工体(p -小体)内的RNA加工。小鼠Lsm14a基因定位于染色体7qB1,全长48.67千碱基(kb),编码一个462个氨基酸的蛋白,与人类Lsm14a具有94.53 %的氨基酸同源性。然而,LSM14A在男性生殖器官中的表达谱及其与男性生育能力的功能相关性尚不清楚。在本研究中,我们报道了LSM14A在小鼠睾丸中表达,并定位于从精原细胞到细长精子的生殖细胞的细胞质中。为了研究LSM14A的功能,我们培育了生殖细胞特异性LSM14A条件敲除(cKO)小鼠。Lsm14a cKO雄性小鼠表现出正常的生长发育和生育能力。Lsm14a cKO睾丸的组织学检查显示保留了精子发生和精管结构。Lsm14a cKO精子形态、顶体完整性和活力正常。睾丸中Lsm14a的缺失并没有显著影响p体的形成,这表明LSM家族其他成员的遗传补偿可能在Lsm14a敲除后被激活,从而补偿了其功能的缺失。总的来说,这些发现表明LSM14A对于小鼠的精子发生和雄性生育能力是必不可少的。
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Cells and Development
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