Cell reports最新文献_第2页

The lysis mechanism of the haloarchaeal virus HFTV1. 盐古细菌病毒HFTV1的裂解机制。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118117

Bastiaan P Kuiper, Marco P A van Tilburg, Leonard E Bäcker, Sourav Maity, Yogy S Ariyanto, Joshua G Petters, Zaloa Aguirre-Sourrouille, Jeroen G Nijland, Harma Karsens, Greetje A Berrelkamp-Lahpor, Colin Tittes, Johanna Wiechert, Julia Frunzke, Bertram Daum, Wouter H Roos, Siewert-J Marrink, Tessa E F Quax

{"title":"The lysis mechanism of the haloarchaeal virus HFTV1.","authors":"Bastiaan P Kuiper, Marco P A van Tilburg, Leonard E Bäcker, Sourav Maity, Yogy S Ariyanto, Joshua G Petters, Zaloa Aguirre-Sourrouille, Jeroen G Nijland, Harma Karsens, Greetje A Berrelkamp-Lahpor, Colin Tittes, Johanna Wiechert, Julia Frunzke, Bertram Daum, Wouter H Roos, Siewert-J Marrink, Tessa E F Quax","doi":"10.1016/j.celrep.2026.118117","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118117","url":null,"abstract":"Tailed bacteriophages can lyse their host with help of the holin-endolysin system. However, for archaeal tailed viruses (arTVs), whose archaeal hosts have a fundamentally different cell envelope, lysis mechanisms are unknown. In this study, we use the model archaeal virus-host system: Haloferax tailed virus 1 (HFTV1), which infects the methanobacteriote Haloferax gibbonsii LR2-5. We identified and characterized the lysis protein GP33, a small membrane protein that has no sequence homology with bacterial holins. Overexpression resulted in cell lysis, and the protein forms foci near the cell envelope. Molecular dynamics simulation suggests that it forms pores from which the lipids are repelled, which might result in cell lysis. Indeed, atomic force microscopy (AFM) showed that GP33 forms pores in membranes, which lead to complete membrane disruption at higher concentrations. With this work, we gain insight into a lysis mechanism from a tailed archaeal virus at the molecular level.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118117"},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NAD⁺ precursor treatment prevents cardiomyopathy but disrupts erythroid maturation in mitochondrial progeria. NAD+前体治疗可预防心肌病，但会破坏线粒体早衰症的红细胞成熟。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-16 DOI: 10.1016/j.celrep.2026.118179

Nahid A Khan, Kati Ahlqvist, Swagat Pradhan, Juan Landoni, Christopher Jackson, Aleksandra Zhaivoron, Riikka Kivelä, Liliya Euro, Anu Suomalainen

引用次数: 0

Genome architecture shapes transcriptional responses to topoisomerase depletion in C. elegans. 基因组结构形成秀丽隐杆线虫拓扑异构酶耗竭的转录反应。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118144

Ana Karina Morao, Almira Chervova, Ana Kotte, Yuya Zhao, Ivano Legnini, Sevinc Ercan, Germano Cecere

{"title":"Genome architecture shapes transcriptional responses to topoisomerase depletion in C. elegans.","authors":"Ana Karina Morao, Almira Chervova, Ana Kotte, Yuya Zhao, Ivano Legnini, Sevinc Ercan, Germano Cecere","doi":"10.1016/j.celrep.2026.118144","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118144","url":null,"abstract":"DNA supercoiling is an intrinsic consequence of transcription that must be resolved to maintain proper gene expression. How supercoiling shapes transcription dynamics in animal genomes remains unclear. Here, we acutely depleted topoisomerases in Caenorhabditis elegans and applied nascent transcription profiling, nuclear RNA sequencing (RNA-seq), histone modification mapping, and long-read sequencing to capture the transcriptional and chromatin responses to topological stress. We find that topoisomerase depletion preferentially inhibits and uncouples expression of convergent genes, while transcription initiation and coordinated expression of divergent genes are comparatively maintained. Topoisomerase degradation hinders transcription elongation globally, resulting in reduced production of longer transcripts and overall shortening of poly(A) tails. These elongation defects are not accompanied by global changes in elongation-associated histone modifications but coincide with modest reductions in promoter and enhancer marks. Our results indicate that genome architecture shapes transcriptional responses to DNA supercoiling, uncovering a topological basis for coordinated gene expression in a multicellular organism.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118144"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering genomic adaptations and climate resilience in the intertidal seagrass Zostera japonica. 解读潮间带海草的基因组适应和气候适应能力。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118148

Hongzhen Wang, Xinqi Li, Jinghua Yang, Yu Zang, Jiayi Xin, Ziqing Wei, Shuo Liang, Song Xue, Wenqin Chen, Qifan Zhang, Xiying Meng, Xuexi Tang, Jun Chen

{"title":"Deciphering genomic adaptations and climate resilience in the intertidal seagrass Zostera japonica.","authors":"Hongzhen Wang, Xinqi Li, Jinghua Yang, Yu Zang, Jiayi Xin, Ziqing Wei, Shuo Liang, Song Xue, Wenqin Chen, Qifan Zhang, Xiying Meng, Xuexi Tang, Jun Chen","doi":"10.1016/j.celrep.2026.118148","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118148","url":null,"abstract":"Seagrasses are coastal foundation species that support ecosystem stability but face increasing global change. Here, we assemble a chromosome-level reference genome for the intertidal seagrass Zostera japonica to investigate adaptive evolution and climate resilience. Comparative genomic analyses reveal features underlying intertidal adaptation, including ion transport, circadian regulation, and stress responses. We identify positively selected genes associated with the transition to marine environments. Population genomic analyses identify strong divergence between northern and southern populations, reflecting deep historical separation, largely independent evolutionary trajectories, and local adaptation. Selection signals are enriched in stress response and ion transport genes, among which TIP3-1 confers tolerance to both salinity and heat. Genomic offset projections indicate greater climate vulnerability in northern populations, whereas southern populations show higher adaptive potential and may serve as genetic sources for assisted gene flow. Together, our study provides a genomic framework for understanding adaptation and guiding conservation under climate change.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118148"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lymphangiogenesis driven by VEGF-C reshapes tumor immune landscape and enables tumor eradication by viral immunotherapy in mouse melanoma models. 在小鼠黑色素瘤模型中，由VEGF-C驱动的淋巴管生成重塑肿瘤免疫景观，并通过病毒免疫治疗实现肿瘤根除。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118130

Ruben Fernandez-Rodriguez, Sara Cuadrado-Castano, Andrew Edwards, Anita Rogic, Yonina Bykov, Ignacio Mena, Noelia Dasilva-Freire, Camila Ceballos Paredes, Alice O Kamphorst, Rosa Karlic, Amir Horowitz, Adolfo García-Sastre, Mihaela Skobe

{"title":"Lymphangiogenesis driven by VEGF-C reshapes tumor immune landscape and enables tumor eradication by viral immunotherapy in mouse melanoma models.","authors":"Ruben Fernandez-Rodriguez, Sara Cuadrado-Castano, Andrew Edwards, Anita Rogic, Yonina Bykov, Ignacio Mena, Noelia Dasilva-Freire, Camila Ceballos Paredes, Alice O Kamphorst, Rosa Karlic, Amir Horowitz, Adolfo García-Sastre, Mihaela Skobe","doi":"10.1016/j.celrep.2026.118130","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118130","url":null,"abstract":"Vascular Endothelial Growth Factor C (VEGF-C), a key lymphangiogenic growth factor, has been implicated in improving responses to cancer immunotherapy. We investigated the impact of VEGF-C on the efficacy of oncolytic virotherapy with avian paramyxoviruses APMV-1 (NDV) and APMV-4. Treatment of B16F10 tumors lacking VEGF-C delays tumor growth, and complete responses (CRs) are rare. In contrast, virotherapy of VEGF-C-expressing tumors leads to CRs in most mice. Rechallenged mice remain tumor- and metastasis-free for over two years, indicating durable immunity. VEGF-C-induced lymphangiogenesis correlates with high CD8+ and CD4+ T cell densities near lymphatic vessels. Spectral flow cytometry shows changes in the composition and activation of CD8+ T cells, CD4+ T cells and NK cells associated with CRs, including enrichment of CD8+CD25+PD-1+ effector T cells. T cell composition changes in sentinel and contralateral lymph nodes, indicating a systemic response. These findings demonstrate that VEGF-C-driven remodeling of the tumor immune microenvironment enables durable CRs to APMV virotherapy.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118130"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ataxin-2 downregulation rewires neuronal and astrocytic metabolism to protect against TDP-43 toxicity. Ataxin-2下调重新连接神经元和星形细胞代谢，以防止TDP-43毒性。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118053

Denise Gastaldo, Stephen Vito, Holly H Black, Oded Foreman, Zhichang Yang, Victoria Pham, Ying Zhu, Meena Choi, Ana Jovičić

{"title":"Ataxin-2 downregulation rewires neuronal and astrocytic metabolism to protect against TDP-43 toxicity.","authors":"Denise Gastaldo, Stephen Vito, Holly H Black, Oded Foreman, Zhichang Yang, Victoria Pham, Ying Zhu, Meena Choi, Ana Jovičić","doi":"10.1016/j.celrep.2026.118053","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118053","url":null,"abstract":"Ataxin-2 (ATXN2) is a genetic modifier of TDP-43 toxicity and a promising therapeutic target in amyotrophic lateral sclerosis (ALS). However, the mechanisms underlying its neuroprotective effects remain poorly understood. Using global proteomic profiling in yeast and mouse TDP-43 models, we establish that pbp1/ataxin-2 (pbp1 is the yeast ataxin-2 ortholog) reduction confers neuroprotection by activating orthogonal stress-adaptive pathways in neurons and glia, rather than simply reversing TDP-43-induced damage. In neurons, ataxin-2 downregulation activates glycolysis and reductive glutamine carboxylation driven by IDH1, restoring ATP production independently of impaired mitochondria. In astrocytes, it upregulates cholesterol biosynthesis via HMGCS1, enhancing trophic support to neurons. Full neuroprotection requires both mechanisms: neuronal survival is only completely rescued when ataxin-2 is reduced in neuron-astrocyte co-cultures. Importantly, ataxin-2 downregulation protects against both TDP-43 gain- and loss-of-function toxicity, broadening its therapeutic relevance. Collectively, these findings establish ataxin-2 as a regulator of stress-adaptive metabolic resilience.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118053"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TDP2-mediated DNA repair regulates the dynamics of neuronal early response gene transcription and cortical neuron connectivity. tdp2介导的DNA修复调节神经元早期反应基因转录和皮质神经元连通性的动态。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118152

Morgan Crewe, Alexander Pope, Ilse Delint-Ramirez, Sandra Fajardo Briseno, Ryan T Stott, Li-Huei Tsai, Kimberly M Huber, Ram Madabhushi

{"title":"TDP2-mediated DNA repair regulates the dynamics of neuronal early response gene transcription and cortical neuron connectivity.","authors":"Morgan Crewe, Alexander Pope, Ilse Delint-Ramirez, Sandra Fajardo Briseno, Ryan T Stott, Li-Huei Tsai, Kimberly M Huber, Ram Madabhushi","doi":"10.1016/j.celrep.2026.118152","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118152","url":null,"abstract":"Neuronal activity induces topoisomerase IIβ (TOP2B) to form DNA double-strand breaks (DSBs) within the promoters of early response genes (ERGs), such as Fos and Npas4, and facilitates rapid ERG transcription. However, the mechanisms that repair activity-induced DSBs and their significance for neuronal function remain ill-defined. Here, we report that depletion of tyrosyl-DNA phosphodiesterase 2 (TDP2) in cultured mouse cortical neurons delays the repair of TOP2B-mediated DSBs and prolongs ERG expression following neuronal stimulation. Deleting Tdp2 in excitatory forebrain neurons in vivo caused DSB accrual, ERG overexpression, and increased excitatory synaptic transmission and cortical circuit dysfunction. Whereas proliferating cells utilize alternative pathways to process TOP2B-mediated DSBs, we find that such mechanisms are relatively inactive in postmitotic neurons. Overall, these results indicate that TDP2-mediated DNA repair is crucial for the temporal control of ERG transcription and suggest that defective repair of activity-induced DSBs could underlie neurological abnormalities in individuals with TDP2 mutations.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118152"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ICAM-1 functions as a functional receptor for encephalomyocarditis virus and reveals a compensatory interplay with ICAM-4. ICAM-1作为脑心肌炎病毒的功能性受体，与ICAM-4具有代偿性相互作用。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118155

Zhengyang Hou, Jingying Xie, Yaxin Zhang, Tianmei Hu, Xiaojing Bao, Xiangrong Li, Yanmei Yang, Huixia Li, Shasha Li, Yanqiao Wen, Ruofei Feng

引用次数: 0

TM6SF2 acts at ER membrane contact sites to enable RAB7-dependent endolysosomal VLDL secretion and maintain Golgi structure. TM6SF2作用于内质网膜接触位点，使rab7依赖性内溶酶体VLDL分泌，维持高尔基结构。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118116

Emad Heidary Arash, Marko Groeger, James P Grenert, Torsten Wittmann, Robert L Raffai, Jacquelyn J Maher, Holger Willenbring

{"title":"TM6SF2 acts at ER membrane contact sites to enable RAB7-dependent endolysosomal VLDL secretion and maintain Golgi structure.","authors":"Emad Heidary Arash, Marko Groeger, James P Grenert, Torsten Wittmann, Robert L Raffai, Jacquelyn J Maher, Holger Willenbring","doi":"10.1016/j.celrep.2026.118116","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118116","url":null,"abstract":"Although a loss-of-function variant of TM6SF2 is a highly penetrant risk factor for steatotic liver disease, including progression to cirrhosis and cancer, its normal function is largely unknown. Here we show that endoplasmic reticulum (ER)-localized TM6SF2 forms membrane contact sites (MCSs) with late endosomes/lysosomes, where it activates the small GTPase RAB7 to enable an endolysosomal route for selective secretion of lipid-rich very low-density lipoprotein (VLDL) particles. In accord, TM6SF2 and RAB7 deficiency similarly cause endolysosomal VLDL retention and accumulation of enlarged late endosomes/lysosomes. TM6SF2 further binds to VAMP-associated protein (VAP) ER-anchor proteins to maintain MCSs between the ER, endosomes, and the trans-Golgi network, with TM6SF2 deficiency causing Golgi fragmentation and disruption of cGAS-STING signaling known to prevent cirrhosis and cancer by clearing senescent hepatocytes. Our findings establish TM6SF2 as an ER-MCS component that enables endolysosomal VLDL secretion and maintains Golgi structure, which suggests that TM6SF2 loss of function causes liver disease through steatosis-dependent and independent mechanisms.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118116"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell analyses reveal lymph node-tumor ecosystem remodeling during lymph node metastasis of gastric cancer. 单细胞分析揭示胃癌淋巴结转移过程中淋巴结-肿瘤生态系统重塑。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-15 DOI: 10.1016/j.celrep.2026.118147

Zhi Zheng, Yuxi Zhang, Zimeng Wang, Bihan Liu, Yuankang Yang, Lehan Pan, Chenglin Xin, Tianzhen Zhang, Rui Xu, Danqing Zhu, Zhongtao Zhang, Yingchi Yang, Jun Zhang, Dan Tian

{"title":"Single-cell analyses reveal lymph node-tumor ecosystem remodeling during lymph node metastasis of gastric cancer.","authors":"Zhi Zheng, Yuxi Zhang, Zimeng Wang, Bihan Liu, Yuankang Yang, Lehan Pan, Chenglin Xin, Tianzhen Zhang, Rui Xu, Danqing Zhu, Zhongtao Zhang, Yingchi Yang, Jun Zhang, Dan Tian","doi":"10.1016/j.celrep.2026.118147","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118147","url":null,"abstract":"Gastric cancer (GC) is a highly aggressive malignancy with a strong propensity for lymph node metastasis. To characterize the metastatic ecosystem, we perform integrated single-cell transcriptomic and T cell receptor profiling of 156,871 cells from 30 primary tumors and matched sentinel lymph nodes (SLNs), spanning non-metastatic and metastatic tumors and SLNs from non-metastatic to micro- and macro-metastatic states. We identify LN-enriched progenitor exhausted T cells as a potential reservoir for tumor-infiltrating exhausted CD8+ T cells and reveal dynamic remodeling of the lymph node microenvironment by tumor-associated macrophages during disease progression. We further show that ILC3s promote a pro-metastatic microenvironment in micro-metastatic lymph nodes through the AREG-EGFR axis, facilitating lymphatic dissemination and subsequent establishment of CD24+ tumor cells. Collectively, these findings provide a stage-resolved view of the tumor-lymph node metastatic ecosystem and identify potential therapeutic targets in GC.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118147"},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0