Molecules and Cells最新文献

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Letter by Kong et al. Regarding Article, “Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knockout, and LacZ knockin mice” Kong等人的信。关于文章《FAM19A5是脂肪因子吗？》外周FAM19A5野生小鼠、FAM19A5敲除小鼠和LacZ敲入小鼠”。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-10-22 DOI: 10.1016/j.mocell.2025.100289

Wei Kong

引用次数: 0

Response to comments by Kong et al. 对Kong等人评论的回应。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-10-17 DOI: 10.1016/j.mocell.2025.100288

Hoyun Kwak , Wijin Jeon , Nui Ha , Soon-Gu Kwon , Jae Young Seong

引用次数: 0

Egr2-dependent Mo-DCs regulate immunosuppressive NK cells, promoting neutrophil-mediated protective immunity against acute Listeria infection egr2依赖性mo - dc调节免疫抑制性NK细胞，促进中性粒细胞介导的抗急性李斯特菌感染的保护性免疫。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-10-16 DOI: 10.1016/j.mocell.2025.100287

Muhammad Umer Ashraf , Myeong-Ho Kang , Yong Taik Lim , Siyoung Yang , Yong-Soo Bae

The interactions between dendritic cells (DCs) and other innate immune cells during acute bacterial infection remain poorly understood. To investigate this cross-talk, we generated CD11c-cre-mediated early growth response gene-2 knockout (Egr2^cKO) mice and used an acute Listeria monocytogenes (LM) infection model. In wild-type mice, LM infection induced the generation of monocyte-derived DCs (Mo-DCs), which suppressed the conversion of natural killer (NK) cells into immunosuppressive NK cells, while Mo-DC-derived TNF-α enhanced neutrophil (NP) activity to control infection. In contrast, Egr2^cKO mice exhibited significantly increased susceptibility to LM infection compared with their Egr2-floxed wild-type littermates, primarily due to a deficiency in Mo-DCs. Instead, monocytes in Egr2^cKO mice differentiated predominantly into macrophages, which expressed interleukin-15/interleukin-15R and promoted the expansion of immunosuppressive CD11b^lowCD27⁺TIGIT⁺ NK cells. These NK cells produced TGF-β, thereby suppressing NP-mediated NETosis. In vivo depletion of NK cells in Egr2^cKO mice partially restored protective immunity, whereas depletion of NPs further exacerbated susceptibility to LM infection. In conclusion, our study demonstrates that Egr2-dependent Mo-DCs play a pivotal role in host defense against acute LM infection by restraining the expansion of immunoregulatory NK cells and enhancing TNF-α-mediated NPs NETosis. These findings highlight the Mo-DC/NK/NP immune axis as a key element of the innate immune response to acute bacterial infection.

急性细菌感染期间树突状细胞（dc）和其他先天免疫细胞之间的相互作用仍然知之甚少。为了研究这种串扰，我们产生了cd11c -cre介导的早期生长反应基因2敲除（Egr2cKO）小鼠，并使用急性单核细胞增生李斯特菌（LM）感染模型。在野生型（WT）小鼠中，LM感染诱导单核细胞来源的dc （mo - dc）的产生，其抑制自然杀伤（NK）细胞向免疫抑制NK细胞的转化，而mo - dc来源的TNF-α增强中性粒细胞（NP）活性以控制感染。相比之下，Egr2cKO小鼠对LM感染的易感性明显增加，这主要是由于缺乏mo - dc。相反，Egr2cKO小鼠中的单核细胞主要分化为巨噬细胞（mo - mac），巨噬细胞表达IL-15/ il - 15r，促进免疫抑制CD11blowCD27+TIGIT+ NK细胞的扩增。这些NK细胞产生TGF-β，从而抑制np介导的NETosis。在Egr2cKO小鼠体内，NK细胞的缺失部分恢复了保护性免疫，而NPs的缺失进一步加剧了对LM感染的易感性。总之，我们的研究表明，依赖egr2的mo - dc通过抑制免疫调节性NK细胞的扩增和增强TNF-α介导的中性粒细胞NETosis，在宿主防御急性LM感染中发挥关键作用。这些发现强调了Mo-DC/NK/NP免疫轴是急性细菌感染先天免疫反应的关键因素。

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引用次数: 0

Approaches to murine T cell isolation and activation 小鼠T细胞的分离和激活方法。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-10-14 DOI: 10.1016/j.mocell.2025.100286

Sangjun Lim , Sohyun Kum , Jin Ouk Choi , Joonbeom Bae , Soo Seok Hwang

In this MiniResource, we outlined practical approaches for preparing murine T cells, from isolation to in vitro activation, with emphasis on reproducibility and viability. While specific experimental conditions should be tailored to individual assays, the principles summarized here provide a framework for establishing robust T cell preparation across diverse research settings. By integrating standard methodologies with troubleshooting insights, this resource aims to support both basic immunological studies and future applications in T cell engineering.

在这个迷你资源中，我们概述了制备小鼠T细胞的实用方法，从分离到体外激活，重点是可重复性和活力。虽然具体的实验条件应该针对个别的分析，这里总结的原则提供了一个框架，在不同的研究环境中建立稳健的T细胞制备。通过将标准方法与故障诊断见解相结合，该资源旨在支持基础免疫学研究和未来在T细胞工程中的应用。

引用次数: 0

Recent preclinical and clinical advances in gene therapy for hereditary hearing loss 基因治疗遗传性听力损失的临床前和临床进展。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-10-12 DOI: 10.1016/j.mocell.2025.100285

Seung Hyun Jang , Hyeong Gi Song , Jinsei Jung , Heon Yung Gee

Hereditary hearing loss is a genetically heterogeneous condition that affects millions of people worldwide and has limited curative treatment options. Recent advancements in gene therapy have opened promising avenues for correcting the underlying genetic defects in the inner ear. This review summarizes the key developments in vector platforms, delivery strategies, target genes, preclinical models, and clinical trials relevant to both gene supplementation and gene editing approaches, as well as future directions. Adeno-associated virus vectors have emerged as the leading platform for inner ear gene transfer, owing to their safety and efficacy. Clinical programs, such as those targeting OTOF variants, are currently underway and are supported by robust preclinical data. Additionally, genome editing technologies, including CRISPR/Cas9-mediated nonhomologous end joining, base editing, and prime editing, offer variant-specific therapeutic potential. Despite these advances, challenges remain in expanding the therapeutic window, ensuring long-term safety, and establishing ethical and regulatory frameworks for their use.

遗传性听力损失是一种遗传异质性疾病，影响着全世界数百万人，治疗选择有限。基因治疗的最新进展为纠正内耳潜在的遗传缺陷开辟了有希望的途径。本文综述了与基因补充和基因编辑方法相关的载体平台、传递策略、靶基因、临床前模型和临床试验的主要进展，以及未来的发展方向。腺相关病毒（AAV）载体由于其安全性和有效性而成为内耳基因转移的主要平台。临床规划，如针对OTOF变异的临床规划，目前正在进行中，并得到了可靠的临床前数据的支持。此外，基因组编辑技术，包括CRISPR/ cas9介导的非同源末端连接、碱基编辑和引物编辑，提供了变异特异性治疗潜力。尽管取得了这些进展，但在扩大治疗窗口、确保长期安全性以及为其使用建立伦理和监管框架方面仍然存在挑战。

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引用次数: 0

Dual SMAD inhibition as a versatile platform in human pluripotent stem cell–based regenerative medicine and disease modeling 双smad抑制作为人类多能干细胞神经科学和再生医学的通用平台。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-10-03 DOI: 10.1016/j.mocell.2025.100284

Lesly Puspita , Magdalena Deline , Jae-won Shim

Dual SMAD inhibition is a robust and widely adopted protocol for directing human pluripotent stem cells (hPSCs) toward neuronal lineages by blocking transforming growth factor–beta and bone morphogenetic protein pathways. Suppressing transforming growth factor–beta and bone morphogenetic protein signaling enables efficient and reproducible induction of neuroectoderm, serving as the foundation for generating diverse brain region–specific neuronal subtypes. This review outlines the mechanistic basis and major achievements of the dual SMAD inhibition strategy, including its application in 2 recent clinical trials for Parkinson’s disease, and its role in preclinical studies targeting conditions, such as spinal cord injury (SCI), retinal degeneration, and amyotrophic lateral sclerosis (ALS). In addition to its significant contribution to the generation of transplantation-ready grafts from hPSCs, the protocol serves as a valuable platform for disease modeling across various neurological and metabolic disorders. The key strengths include high efficiency, technical simplicity that enables precise control of cell fate using small molecules, versatility in both 2- and 3-dimensional culture systems, and reproducibility across various hPSC lines. This review also addresses key limitations, such as restricted gliogenic capacity and limited neural progenitor cell expansion. Future research should focus on incorporating emerging technologies to advance stem cell–based applications. Overall, dual SMAD inhibition represents a powerful and versatile platform for stem cell–based neuroscience and regenerative medicine.

双SMAD抑制是通过阻断转化生长因子- β和骨形态发生蛋白途径引导人类多能干细胞（hPSCs）向神经元谱系发展的一种强大且广泛采用的方案。抑制TGF-β和BMP信号可以有效、可重复地诱导神经外胚层，为产生多种脑区域特异性神经元亚型奠定基础。本文综述了双SMAD抑制策略的机制基础和主要成果，包括其在最近两项帕金森病临床试验中的应用，以及其在针对脊髓损伤、视网膜变性和肌萎缩侧索硬化症等疾病的临床前研究中的作用。除了对从造血干细胞产生移植就绪移植物的重大贡献外，该方案还为各种神经和代谢疾病的疾病建模提供了宝贵的平台。其主要优势包括效率高，技术简单，可以使用小分子精确控制细胞命运，在二维和三维培养系统中的通用性，以及在各种hPSC系中的可重复性。这篇综述也指出了关键的局限性，如限制胶质细胞生成能力和限制神经祖细胞扩增。未来的研究应该集中于结合新兴技术来推进基于干细胞的应用。总的来说，双重SMAD抑制为干细胞神经科学和再生医学提供了一个强大而通用的平台。

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引用次数: 0

GOREA: Unbiased Interpretation of Functional Enrichment 基因本体富集的系统和公正解释框架。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-09-24 DOI: 10.1016/j.mocell.2025.100283

Hojin Lee, Young-In Park, Ina Jeon, Dawon Kang, Harim Chun, Jungmin Choi

Functional enrichment analysis is essential for extracting biological meaning from gene expression data. Gene set enrichment analysis (GSEA) and over-representation analysis (ORA) are widely used approaches for this purpose. However, interpreting the large number of enriched gene ontology biological process (GOBP) terms remains challenging. Existing tools such as simplifyEnrichment often yield overly general and fragmented keywords, and they do not effectively utilize quantitative metrics such as normalized enrichment scores (NES) or gene overlap proportions, thereby limiting biological interpretation and prioritization. To address these issues, we developed GOREA, an improved tool for summarizing GOBP terms. GOREA improves upon simplifyEnrichment by integrating binary cut and hierarchical clustering, incorporating GOBP term hierarchy to define representative terms, and ranking clusters based on NES or gene overlap proportions. Using ComplexHeatmap R package, GOREA visualizes results as a heatmap accompanied by a panel of broad GOBP terms and representative terms for each cluster, providing both general and specific biological insights. Compared to simplifyEnrichment, GOREA yields more specific and interpretable clusters while significantly reducing computational time. GOREA effectively identified distinct biological processes in immune-related data and revealed substantial overlap between GOBP terms and cancer hallmark gene sets, demonstrating its applicability across diverse biological contexts. These findings suggest that GOREA provides a substantial improvement over existing approaches and offers a scalable and efficient framework for GSEA and ORA across diverse biological contexts.

功能富集分析是从基因表达数据中提取生物学意义的关键。基因集富集分析（GSEA）和过度代表性分析（ORA）是广泛使用的方法。然而，解释大量丰富的基因本体生物过程（GOBP）术语仍然具有挑战性。现有的工具，如simplifyEnrichment，往往产生过于笼统和碎片化的关键词，它们不能有效地利用定量指标，如标准化浓缩分数（NES）或基因重叠比例，从而限制了生物学解释和优先级。为了解决这些问题，我们开发了GOREA，这是一个用于总结GOBP术语的改进工具。GOBP在简化浓缩的基础上进行了改进，整合了二元分割和层次聚类，结合GOBP术语层次来定义代表性术语，并基于NES或基因重叠比例对聚类进行排序。使用ComplexHeatmap包，GOREA将结果可视化为热图，并附有一组广泛的GOBP术语和每个集群的代表性术语，提供一般和特定的生物学见解。与simplifyEnrichment相比，GOREA产生更具体和可解释的聚类，同时显着减少了计算时间。GOREA有效地识别了免疫相关数据中不同的生物学过程，并揭示了GOBP术语和癌症标志基因集之间的大量重叠，证明了其在不同生物学背景下的适用性。这些发现表明，GOREA提供了对现有方法的实质性改进，并为跨不同生物背景的基因集富集分析提供了一个可扩展和有效的框架。

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引用次数: 0

Immune cell isolation from lymphoid and nonlymphoid organs 淋巴和非淋巴器官的免疫细胞分离。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-09-19 DOI: 10.1016/j.mocell.2025.100277

Jong Seok Park, Yoontae Lee

Immune cells are distributed across various tissues. While a majority are concentrated in primary and secondary lymphoid organs such as the bone marrow, thymus, lymph nodes, and spleen, a subset resides in nonlymphoid organs, including the kidney, liver, and lung, as well as the peritoneal cavity, where they play critical roles in local immune surveillance and response. In this editorial, we outline concise and practical protocols for the isolation of immune cells from a range of lymphoid and nonlymphoid organs.

免疫细胞分布在各种组织中。虽然大多数集中在原发性和继发性淋巴器官，如骨髓、胸腺、淋巴结和脾脏，但有一部分存在于非淋巴器官，包括肾、肝、肺和腹腔，它们在局部免疫监视和反应中起关键作用。在这篇社论中，我们概述了从一系列淋巴和非淋巴器官中分离免疫细胞的简明和实用的方案。

引用次数: 0

Editorial Board Members/Copyright 编辑委员会成员/版权

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-09-18 DOI: 10.1016/S1016-8478(25)00104-9

引用次数: 0

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IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-09-18 DOI: 10.1016/S1016-8478(25)00103-7

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