Cell Discovery最新文献

Author Correction: Single-cell and spatial proteo-transcriptomic profiling reveals immune infiltration heterogeneity associated with neuroendocrine features in small cell lung cancer.

IF 13 1区生物学

Cell Discovery Pub Date : 2024-12-19 DOI: 10.1038/s41421-024-00755-z

Ying Jin, Yuefeng Wu, Alexandre Reuben, Liang Zhu, Carl M Gay, Qingzhe Wu, Xintong Zhou, Haomin Mo, Qi Zheng, Junyu Ren, Zhaoyuan Fang, Teng Peng, Nan Wang, Liang Ma, Yun Fan, Hai Song, Jianjun Zhang, Ming Chen

引用次数: 0

Packaged release and targeted delivery of cytokines by migrasomes in circulation.

IF 13 1区生物学

Cell Discovery Pub Date : 2024-12-09 DOI: 10.1038/s41421-024-00749-x

Haifeng Jiao, Xiaopeng Li, Ying Li, Ziyi Guo, Yuzhuo Yang, Yiqun Luo, Xiaoyu Hu, Li Yu

{"title":"Packaged release and targeted delivery of cytokines by migrasomes in circulation.","authors":"Haifeng Jiao, Xiaopeng Li, Ying Li, Ziyi Guo, Yuzhuo Yang, Yiqun Luo, Xiaoyu Hu, Li Yu","doi":"10.1038/s41421-024-00749-x","DOIUrl":"10.1038/s41421-024-00749-x","url":null,"abstract":"In dynamic systems like the circulatory system, establishing localized cytokine gradients is challenging. Upon lipopolysaccharide (LPS) stimulation, we observed that monocytes release numerous migrasomes enriched with inflammatory cytokines, such as TNF-α and IL-6. These cytokines are transported into migrasomes via secretory carriers, leading to their immediate exocytosis or eventual release from detached migrasomes. We successfully isolated TNF-α and IL-6-enriched, monocyte-derived migrasomes from the blood of LPS-treated mice. Total secretion analysis revealed a substantial amount of TNF-α and IL-6 released in a migrasome-packaged form. Thus, detached, monocyte-derived migrasomes represent a type of extracellular vesicle highly enriched with cytokines. Physiologically, these cytokine-laden migrasomes rapidly accumulate at local sites of inflammation, effectively creating a concentrated source of cytokines. Our research uncovers novel mechanisms for cytokine release and delivery, providing new insights into immune response modulation.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"121"},"PeriodicalIF":13.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The comprehensive SARS-CoV-2 'hijackome' knowledge base.

IF 13 1区生物学

Cell Discovery Pub Date : 2024-12-09 DOI: 10.1038/s41421-024-00748-y

Sini Huuskonen, Xiaonan Liu, Ina Pöhner, Taras Redchuk, Kari Salokas, Rickard Lundberg, Sari Maljanen, Milja Belik, Arttu Reinholm, Pekka Kolehmainen, Antti Tuhkala, Garima Tripathi, Pia Laine, Sergei Belanov, Petri Auvinen, Maria Vartiainen, Salla Keskitalo, Pamela Österlund, Larissa Laine, Antti Poso, Ilkka Julkunen, Laura Kakkola, Markku Varjosalo

{"title":"The comprehensive SARS-CoV-2 'hijackome' knowledge base.","authors":"Sini Huuskonen, Xiaonan Liu, Ina Pöhner, Taras Redchuk, Kari Salokas, Rickard Lundberg, Sari Maljanen, Milja Belik, Arttu Reinholm, Pekka Kolehmainen, Antti Tuhkala, Garima Tripathi, Pia Laine, Sergei Belanov, Petri Auvinen, Maria Vartiainen, Salla Keskitalo, Pamela Österlund, Larissa Laine, Antti Poso, Ilkka Julkunen, Laura Kakkola, Markku Varjosalo","doi":"10.1038/s41421-024-00748-y","DOIUrl":"10.1038/s41421-024-00748-y","url":null,"abstract":"The continuous evolution of SARS-CoV-2 has led to the emergence of several variants of concern (VOCs) that significantly affect global health. This study aims to investigate how these VOCs affect host cells at proteome level to better understand the mechanisms of disease. To achieve this, we first analyzed the (phospho)proteome changes of host cells infected with Alpha, Beta, Delta, and Omicron BA.1 and BA.5 variants over time frames extending from 1 to 36 h post infection. Our results revealed distinct temporal patterns of protein expression across the VOCs, with notable differences in the (phospho)proteome dynamics that suggest variant-specific adaptations. Specifically, we observed enhanced expression and activation of key components within crucial cellular pathways such as the RHO GTPase cycle, RNA splicing, and endoplasmic reticulum-associated degradation (ERAD)-related processes. We further utilized proximity biotinylation mass spectrometry (BioID-MS) to investigate how specific mutation of these VOCs influence viral-host protein interactions. Our comprehensive interactomics dataset uncovers distinct interaction profiles for each variant, illustrating how specific mutations can change viral protein functionality. Overall, our extensive analysis provides a detailed proteomic profile of host cells for each variant, offering valuable insights into how specific mutations may influence viral protein functionality and impact therapeutic target identification. These insights are crucial for the potential use and design of new antiviral substances, aiming to enhance the efficacy of treatments against evolving SARS-CoV-2 variants.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"125"},"PeriodicalIF":13.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TPM4 condensates glycolytic enzymes and facilitates actin reorganization under hyperosmotic stress.

IF 13 1区生物学

Cell Discovery Pub Date : 2024-12-03 DOI: 10.1038/s41421-024-00744-2

Wenzhong Yang, Yuan Wang, Geyao Liu, Yan Wang, Congying Wu

{"title":"TPM4 condensates glycolytic enzymes and facilitates actin reorganization under hyperosmotic stress.","authors":"Wenzhong Yang, Yuan Wang, Geyao Liu, Yan Wang, Congying Wu","doi":"10.1038/s41421-024-00744-2","DOIUrl":"10.1038/s41421-024-00744-2","url":null,"abstract":"Actin homeostasis is fundamental for cell structure and consumes a large portion of cellular ATP. It has been documented in the literature that certain glycolytic enzymes can interact with actin, indicating an intricate interplay between the cytoskeleton and cellular metabolism. Here we report that hyperosmotic stress triggers actin severing and subsequent phase separation of the actin-binding protein tropomyosin 4 (TPM4). TPM4 condensates recruit glycolytic enzymes such as HK2, PFKM, and PKM2, while wetting actin filaments. Notably, the condensates of TPM4 and glycolytic enzymes are enriched of NADH and ATP, suggestive of their functional importance in cell metabolism. At cellular level, actin filament assembly is enhanced upon hyperosmotic stress and TPM4 condensation, while depletion of TPM4 impairs osmolarity-induced actin reorganization. At tissue level, colocalized condensates of TPM4 and glycolytic enzymes are observed in renal tissues subjected to hyperosmotic stress. Together, our findings suggest that stress-induced actin perturbation may act on TPM4 to organize glycolytic hubs that tether energy production to cytoskeletal reorganization.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"120"},"PeriodicalIF":13.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic recording of transient endothelial activation in distinct alveolar capillary cells during pulmonary fibrosis.

IF 13 1区生物学

Cell Discovery Pub Date : 2024-12-03 DOI: 10.1038/s41421-024-00745-1

Hongxin Li, Shaohua Zhang, Xiuzhen Huang, Zhenqian Zhang, Kuo Liu, Qing-Dong Wang, Alex F Chen, Kathy O Lui, Kun Sun, Bin Zhou

引用次数: 0

Unveiling potential threats: backdoor attacks in single-cell pre-trained models.

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-30 DOI: 10.1038/s41421-024-00753-1

Sicheng Feng, Siyu Li, Luonan Chen, Shengquan Chen

引用次数: 0

Structural insights into physiological activation and antagonism of melanin-concentrating hormone receptor MCHR1.

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-30 DOI: 10.1038/s41421-024-00754-0

Xiaofan Ye, Guibing Liu, Xiu Li, Binbin He, Yuyong Tao, Jiasheng Guan, Yuguang Mu, Haiping Liu, Weimin Gong

引用次数: 0

Structural and molecular basis of the epistasis effect in enhanced affinity between SARS-CoV-2 KP.3 and ACE2.

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-30 DOI: 10.1038/s41421-024-00752-2

Leilei Feng, Zhaoxi Sun, Yuchen Zhang, Fanchong Jian, Sijie Yang, Keely Xia, Lingling Yu, Jing Wang, Fei Shao, Xiangxi Wang, Yunlong Cao

引用次数: 0

Structural mechanisms of human sodium-coupled high-affinity choline transporter CHT1. 人类钠偶联高亲和性胆碱转运体 CHT1 的结构机制。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-26 DOI: 10.1038/s41421-024-00731-7

Jing Xue, Hongwen Chen, Yong Wang, Youxing Jiang

{"title":"Structural mechanisms of human sodium-coupled high-affinity choline transporter CHT1.","authors":"Jing Xue, Hongwen Chen, Yong Wang, Youxing Jiang","doi":"10.1038/s41421-024-00731-7","DOIUrl":"10.1038/s41421-024-00731-7","url":null,"abstract":"Mammalian sodium-coupled high-affinity choline transporter CHT1 uptakes choline in cholinergic neurons for acetylcholine synthesis and plays a critical role in cholinergic neurotransmission. Here, we present the high-resolution cryo-EM structures of human CHT1 in apo, substrate- and ion-bound, hemicholinium-3-inhibited, and ML352-inhibited states. These structures represent three distinct conformational states, elucidating the structural basis of the CHT1-mediated choline uptake mechanism. Three ion-binding sites, two for Na+ and one for Cl-, are unambiguously defined in the structures, demonstrating that both ions are indispensable cofactors for high-affinity choline-binding and are likely transported together with the substrate in a 2:1:1 stoichiometry. The two inhibitor-bound CHT1 structures reveal two distinct inhibitory mechanisms and provide a potential structural platform for designing therapeutic drugs to manipulate cholinergic neuron activity. Combined with the functional analysis, this study provides a comprehensive view of the structural mechanisms underlying substrate specificity, substrate/ion co-transport, and drug inhibition of a physiologically important symporter.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"116"},"PeriodicalIF":13.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression. 对瘤内微生物群的特征描述显示，血管链球菌会增加胃癌发生和发展的风险。

IF 13 1区生物学

Cell Discovery Pub Date : 2024-11-26 DOI: 10.1038/s41421-024-00746-0

Li Yuan, Libin Pan, Yunzhe Wang, Jing Zhao, Luo Fang, Ying Zhou, Ruihong Xia, Yubo Ma, Zhengchen Jiang, Zhiyuan Xu, Can Hu, Yanan Wang, Shengjie Zhang, Bo Zhang, Haiying Ding, Mengxuan Chen, Haibo Cheng, Ajay Goel, Zhao Zhang, Xiangdong Cheng

{"title":"Characterization of the landscape of the intratumoral microbiota reveals that Streptococcus anginosus increases the risk of gastric cancer initiation and progression.","authors":"Li Yuan, Libin Pan, Yunzhe Wang, Jing Zhao, Luo Fang, Ying Zhou, Ruihong Xia, Yubo Ma, Zhengchen Jiang, Zhiyuan Xu, Can Hu, Yanan Wang, Shengjie Zhang, Bo Zhang, Haiying Ding, Mengxuan Chen, Haibo Cheng, Ajay Goel, Zhao Zhang, Xiangdong Cheng","doi":"10.1038/s41421-024-00746-0","DOIUrl":"10.1038/s41421-024-00746-0","url":null,"abstract":"As a critical component of the tumour immune microenvironment (TIME), the resident microbiota promotes tumorigenesis across a variety of cancer types. Here, we integrated multiple types of omics data, including microbiome, transcriptome, and metabolome data, to investigate the functional role of intratumoral bacteria in gastric cancer (GC). The microbiome was used to categorize GC samples into six subtypes, and patients with a high abundance of Streptococcus or Pseudomonas had a markedly worse prognosis. Further assays revealed that Streptococcus anginosus (SA) promoted tumour cell proliferation and metastasis while suppressing the differentiation and infiltration of CD8+ T cells. However, antibiotic treatment significantly suppressed tumorigenesis in SA+ mice in vivo. We further demonstrated that the SA arginine pathway increased the abundance of ornithine, which may be a major contributor to reshaping of the TIME. Our findings demonstrated that SA, a novel risk factor, plays significant roles in the initiation and progression of GC, suggesting that SA might be a promising target for the diagnosis and treatment of GC.","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"117"},"PeriodicalIF":13.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0