Molecules and Cells最新文献

英文中文

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 : 2025-12-01 Epub 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

Ionotropic receptors mediate arachidic acid perception and food avoidance behavior in Drosophila melanogaster 嗜离子受体介导黑腹果蝇花生酸感知和食物回避行为。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-12-01 Epub Date: 2025-11-03 DOI: 10.1016/j.mocell.2025.100290

Roshani Nhuchhen Pradhan, Muhammad Atif, Youngseok Lee

Chemosensory functions are essential for animals to distinguish between nutritious and harmful compounds. Fatty acids are vital dietary components, but their taste perception mechanisms remain poorly understood. In Drosophila melanogaster, we identified a cluster of ionotropic receptors (IR7g, IR25a, IR51b, IR67a, and IR76b) that mediate the detection of the long-chain saturated fatty acid, arachidic acid (ARCH), through bitter-sensing gustatory receptor neurons. Our findings demonstrate that high doses of ARCH elicit strong aversive responses and exhibit toxic effects, decreasing survival rates in a dose-dependent manner. ARCH detection was found to require the activation of bitter-sensing gustatory receptor neurons, and the inhibition of sugar-sensing neurons contributed to diminished feeding responses. This study provides critical insights into the molecular and neural mechanisms underlying fatty acid perception in Drosophila, opening new avenues for understanding how animals manage dietary lipid intake and its implications for health.

化学感觉功能对动物区分营养物质和有害物质至关重要。脂肪酸是重要的饮食成分，但其味觉感知机制仍然知之甚少。在黑腹果蝇中，我们发现了一组嗜离子受体（IR7g、IR25a、IR51b、IR67a和IR76b），它们通过苦味感知味觉受体神经元（grn）介导长链饱和脂肪酸花生酸（ARCH）的检测。我们的研究结果表明，高剂量的ARCH引起强烈的厌恶反应，并表现出毒性作用，以剂量依赖的方式降低生存率。ARCH检测需要激活苦味感知神经元，而糖感知神经元的抑制导致了摄食反应的减弱。这项研究为果蝇脂肪酸感知的分子和神经机制提供了重要的见解，为理解动物如何管理饮食脂质摄入及其对健康的影响开辟了新的途径。

引用次数: 0

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 : 2025-12-01 Epub Date: 2025-10-22 DOI: 10.1016/j.mocell.2025.100289

Wei Kong

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 : 2025-12-01 Epub 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

THRAISE: An automated and reproducible web platform for RNA-seq analysis THRAISE：用于RNA-seq分析的自动化和可重复的网络平台。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-12-01 Epub Date: 2025-11-13 DOI: 10.1016/j.mocell.2025.100299

Hyeon Ho Heo, Soo-Jong Um

Transcriptome-wide High-throughput RNA-seq Analysis Integrated System is a highly streamlined web platform for RNA-seq analysis that requires no programming expertise. Starting from raw NCBI Sequence Read Archive data, it performs the entire analysis pipeline, which includes quality control, alignment, quantification, differential expression, and functional enrichment using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and Gene Set Enrichment Analysis. For datasets with limited replicates (n = 1), an alternative workflow is also provided, based on transcripts per million. With real-time monitoring, interactive visualization, and a user-friendly interface, Transcriptome-wide High-throughput RNA-seq Analysis Integrated System enables accessible and reproducible RNA-seq analysis for all researchers.

THRAISE（转录组全范围高通量RNA-seq分析集成系统）是一个高度精简的RNA-seq分析网络平台，不需要编程专业知识。从原始NCBI SRA数据开始，使用GO、KEGG、Reactome和GSEA执行整个分析流程，包括质量控制、比对、定量、差异表达和功能富集。对于具有有限复制（n = 1）的数据集，还提供了基于每百万副本（TPM）的替代工作流。THRAISE具有实时监测，交互式可视化和用户友好的界面，可为所有研究人员提供可访问和可重复的RNA-seq分析。

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 : 2025-12-01 Epub 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

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 : 2025-11-01 Epub 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

Decoding genomic rearrangements for cancer driver discovery 解码癌症中的基因组重排：新驱动发现之路。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-11-01 Epub Date: 2025-08-30 DOI: 10.1016/j.mocell.2025.100272

Enyoung Seo , Sooyeon Park , Inho Park , Jinhyuk Bhin

Somatically acquired genomic rearrangements are common genomic alterations that contribute to malignancy by altering the expression or activity of cancer-related genes in human cancer. Genomic rearrangements play a crucial role in tumor development by contributing to driver events in approximately 25% of cancer patients. Most rearrangements are nonrecurrent and lack functional impact. However, some rearrangements produce functional transcripts and act as cancer drivers that may be therapeutic targets. The growing availability of whole-genome and matched RNA-sequencing data from large patient cohorts offers tremendous opportunities to identify novel, clinically relevant drivers arising from genomic rearrangements. In this review, we summarize current knowledge of driver rearrangements as therapeutic targets and highlight recent discoveries of functional transcripts such as intergenic fusions generated by noncanonical rearrangements. We also discuss computational approaches to decode rearrangement patterns and leverage large-scale whole-genome data to discover novel drivers.

体细胞获得性基因组重排是通过改变人类癌症相关基因的表达或活性而导致恶性肿瘤的常见基因组改变。在大约25%的癌症患者中，基因组重排在肿瘤发展中起着至关重要的作用。大多数重排是非经常性的，缺乏功能影响。然而，一些重排产生功能性转录本，并作为可能成为治疗靶点的癌症驱动因子。来自大型患者队列的全基因组和匹配rna测序数据的不断增加，为鉴定基因组重排引起的新的临床相关驱动因素提供了巨大的机会。在这篇综述中，我们总结了驱动重排作为治疗靶点的现有知识，并强调了最近发现的功能性转录本，如由非规范重排产生的基因间融合。我们还讨论了解码重排模式的计算方法，并利用大规模全基因组数据来发现新的驱动因素。

引用次数: 0

Charge-dependent localization of Toll-like receptor 5 at the plasma membrane toll样受体5在质膜上的电荷依赖定位。

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells

Pub Date : 2025-11-01 Epub Date: 2025-09-05 DOI: 10.1016/j.mocell.2025.100275

Ji-Won Huh , Kwangcheon Park , Hyun-Sup Song , Seongryong Kim , You-Me Kim

Proper subcellular localization of Toll-like receptors (TLRs) is essential for initiating appropriate innate immune responses against pathogens while avoiding self-reactivity. Unc-93 homolog B1 (UNC93B1) is known to mediate the intracellular trafficking of nucleotide-sensing TLRs such as TLR9 which undergoes rapid internalization into endolysosomes upon reaching the cell surface. We previously demonstrated that UNC93B1 also facilitates the plasma membrane localization of TLR5, a sensor for bacterial flagellin. Unlike TLR9, TLR5 remained stably at the cell surface under steady-state conditions, suggesting the involvement of distinct sorting mechanisms. Using mutagenesis-based approaches, we found that the cytoplasmic domain of TLR5 is required for its surface retention, whereas the cytoplasmic domain of TLR9 is dispensable for internalization. Notably, TLR5 contains polybasic residues in its C-terminal region, absent in other TLRs. Deletion or alanine substitution of these residues led to constitutive endocytosis of TLR5. Conversely, appending the TLR5 C-terminal region to the C-terminus of TLR9 promoted its surface accumulation. Moreover, when the TLR5 C-terminal sequence was fused to a cytosolic protein along with a myristoylation motif, it mediated membrane association of the cytosolic protein in a charge-dependent manner. We further found that this region can directly interact with phosphatidic acid, an anionic phospholipid enriched in the plasma membrane. These findings reveal an electrostatic mechanism by which TLR5 is selectively retained at the plasma membrane, providing new insight into receptor-specific localization of TLRs.

toll样受体（TLRs）的适当亚细胞定位对于启动针对病原体的适当先天免疫反应而避免自身反应是必不可少的。已知UNC93B1介导TLR9等核苷酸敏感tlr的细胞内运输，TLR9在到达细胞表面后迅速内化到内溶酶体中。我们之前证明了UNC93B1也促进了TLR5的质膜定位，TLR5是细菌鞭毛蛋白的传感器。与TLR9不同，在稳态条件下，TLR5在细胞表面保持稳定，表明其参与了不同的分选机制。使用基于诱变的方法，我们发现TLR5的胞质结构域是其表面保留所必需的，而TLR9的胞质结构域是其内化所必需的。值得注意的是，TLR5在其c端区域含有多碱基残基，这在其他tlr中是不存在的。这些残基的缺失或丙氨酸取代导致TLR5的组成性内吞作用。相反，将TLR5的c端区域附加到TLR9的c端，则促进了TLR9的表面积累。此外，当TLR5 c端序列与肉豆蔻酰化基序融合到胞质蛋白时，它以电荷依赖的方式介导了胞质蛋白的膜结合。我们进一步发现该区域可以直接与磷脂酸相互作用，磷脂酸是一种富含质膜的阴离子磷脂。这些发现揭示了TLR5选择性保留在质膜上的静电机制，为tlr的受体特异性定位提供了新的见解。资料可得性：支持本研究结果的所有数据均可在主稿件和补充信息文件中获得。

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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 : 2025-11-01 Epub 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。

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