Cell reports最新文献_第4页

Macrophage-induced ferritin expression protects pancreatic cancer cells from ferroptosis. 巨噬细胞诱导的铁蛋白表达保护胰腺癌细胞免于铁下垂。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118079

Eric C Cheung, Meng-Han Wu, Wen-Chi Cheng, Jack Coomes, Karen Blyth, Karen H Vousden

{"title":"Macrophage-induced ferritin expression protects pancreatic cancer cells from ferroptosis.","authors":"Eric C Cheung, Meng-Han Wu, Wen-Chi Cheng, Jack Coomes, Karen Blyth, Karen H Vousden","doi":"10.1016/j.celrep.2026.118079","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118079","url":null,"abstract":"Reactive oxygen species (ROS) drive pro-tumorigenic signaling but also promote lipid peroxidation and ferroptosis, making ROS regulation critical during high oxidative stress stages of tumor progression, such as metastasis. Loss of the antioxidant TIGAR in pancreatic ductal adenocarcinoma (PDAC) cells raises ROS and enhances metastatic behavior but also sensitizes cells to ferroptosis. To understand how TIGAR-null cells survive to metastasize, we examine the role of macrophage infiltration, which is increased in TIGAR-null tumors. Co-culturing TIGAR-null PDAC cells with macrophages protects them from ferroptosis. The tumor cells induce macrophage IL-6 secretion, which leads to the activation of STAT3 and upregulation of the iron-sequestering protein ferritin (FTH1) in cancer cells. FTH1 depletion in TIGAR-null cells restores ferroptosis sensitivity and reduces lung metastasis. These results suggest that the outcome of increased ROS in tumors may depend on the activation of mechanisms that selectively prevent ferroptosis while preserving ROS-induced oncogenic signaling and metastasis-promoting pathways.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118079"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179469","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

A systemic circadian nicotinic acid riboside (NaR) signal engages the unfolded protein response and adipogenesis via the prefoldin complex. 系统性昼夜节律烟酸核苷（NaR）信号通过前折叠蛋白复合物参与未折叠蛋白反应和脂肪形成。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118136

Ivan Vlassakev, Christina Savva, Liying Zhou, Danilo Ritz, Alexander Schmidt, Cholsoon Jang, Amir Ata Saei, Paul Petrus

{"title":"A systemic circadian nicotinic acid riboside (NaR) signal engages the unfolded protein response and adipogenesis via the prefoldin complex.","authors":"Ivan Vlassakev, Christina Savva, Liying Zhou, Danilo Ritz, Alexander Schmidt, Cholsoon Jang, Amir Ata Saei, Paul Petrus","doi":"10.1016/j.celrep.2026.118136","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118136","url":null,"abstract":"Daily light-dark cycles impose environmental fluctuations that require coordinated regulation of physiology. This coordination is mediated by the circadian clock, which operates as a network of tissue oscillators; however, the signals that convey circadian information between organs remain incompletely defined. We identify nicotinic acid riboside (NaR) as a circulating metabolite whose rhythmicity depends on the liver clock. In adipocytes and neuronal cells, NaR engages the unfolded protein response (UPR). Proteome-wide stability profiling implicates the prefoldin complex as a target of NaR, linking NaR exposure to altered proteostasis. In adipocytes, NaR-induced UPR signaling converges on the transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). Sustained NaR exposure suppresses adipocyte lipid deposition, whereas temporally restricted NaR stimulation enhances adipogenesis. Together, these findings identify NaR as a liver clock-controlled circulating metabolite that couples systemic circadian metabolism to proteostasis and tissue remodeling, revealing a mechanism by which temporal metabolic signals shape tissue-specific physiological outcomes.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118136"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179448","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

Anterior cingulate feedback facilitates rapid global context modulation in primary visual cortex. 前扣带反馈促进初级视觉皮层快速全局情境调节。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118151

Darcy S Peterka, Fumiyasu Imai, Jordan M Ross, Georgia Bastos, Molly A Hornick, Lital Rachmany, Connor G Gallimore, Adam Hockley, Jordan P Hamm

{"title":"Anterior cingulate feedback facilitates rapid global context modulation in primary visual cortex.","authors":"Darcy S Peterka, Fumiyasu Imai, Jordan M Ross, Georgia Bastos, Molly A Hornick, Lital Rachmany, Connor G Gallimore, Adam Hockley, Jordan P Hamm","doi":"10.1016/j.celrep.2026.118151","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118151","url":null,"abstract":"Context modulates sensory processing. Recent proposals claim early areas like primary visual cortex (V1) are only influenced by \"local\" context (e.g., recent stimulus history), while \"global\" context (e.g., learned patterns and probabilities) modulates only higher areas. We tested this using a global/local oddball paradigm: mice viewed repeating five-item sequences (AAAA-B), where B is deviant from local context but typical in global context. Using two-photon imaging and local field potential (LFP) recording in mouse V1, we found that global predictability normalized responses to B stimuli. This effect emerged after fewer than 10 sequence repetitions, demonstrating rapid learning. When a globally deviant \"C\" stimulus replaced B or when B occurred at unpredictable intervals (i.e., standard oddball), V1 showed strong response enhancement. This global context modulation in V1 required top-down feedback from anterior cingulate area. However, when B was replaced by an A (AAAA-A), responses were mixed, suggesting that stimulus-specific adaptation can constrain prediction-error signals in V1.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118151"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179515","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

Molecular mechanisms of promoter silencing by transcriptional readthrough. 启动子沉默的转录解读分子机制。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118139

Gerry A Shipman, Erika Walback, Andy García González, Cynthia Horth, Michel Gravel, Eric Bareke, Jacek Majewski

{"title":"Molecular mechanisms of promoter silencing by transcriptional readthrough.","authors":"Gerry A Shipman, Erika Walback, Andy García González, Cynthia Horth, Michel Gravel, Eric Bareke, Jacek Majewski","doi":"10.1016/j.celrep.2026.118139","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118139","url":null,"abstract":"Transcriptional interference is the in cis suppression of one transcriptional process by another. To define the mechanisms by which transcriptional readthrough is converted into stable gene silencing, we develop a mouse cell line model of cobalamin C deficiency associated with MMACHC silencing (epi-cblC) by deleting the Prdx1 intron 5 splice acceptor, thereby inducing antisense transcription across Mmachc. Readthrough results in ectopic H3K36me3 deposition, de novo DNA methylation, and stable silencing of Mmachc. Through systematic perturbations of transcription and the H3K36 and DNA methylation machinery, we demonstrate that antisense transcription is the primary driver of repression, whereas H3K36me3 contributes directly to promoter silencing and is further required for the establishment of DNA methylation, which in turn confers long-term stability. Together, these findings define a hierarchical silencing cascade by which transcriptional readthrough establishes stable gene repression and demonstrate that transcription itself can direct local chromatin remodeling and changes in gene expression.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118139"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179525","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

Quantifying the impact of genetic mutations on enhancer dynamics. 量化基因突变对增强子动力学的影响。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118131

Maitreya Das, Deepro Banerjee, Ayaan Hossain, Matthew Jensen, Saie Mogre, Jiawan Sun, Joseph Mao, Adam B Glick, Howard M Salis, Santhosh Girirajan

{"title":"Quantifying the impact of genetic mutations on enhancer dynamics.","authors":"Maitreya Das, Deepro Banerjee, Ayaan Hossain, Matthew Jensen, Saie Mogre, Jiawan Sun, Joseph Mao, Adam B Glick, Howard M Salis, Santhosh Girirajan","doi":"10.1016/j.celrep.2026.118131","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118131","url":null,"abstract":"Transcriptional regulation is mediated by enhancers, yet how genetic perturbations alter enhancer activity and gene expression remains unclear. We develop UDI-UMI-STARR-seq, integrating dual indexes and unique molecular identifiers, and combine it with RNA-seq to profile perturbation-associated changes in enhancer activity and gene expression. We apply this approach to 253,632 fragments representing 46,142 cell type-specific candidate enhancers and assess the impact of CRISPR/Cas9-mediated deletion of six transcription factors (ATF2, CTCF, FOXA1, LEF1, TCF7L2, and SCRT1). We identify responsive fragments that are repressed or induced and enriched for p53 family motifs. Enhancer-gene mapping reveals associations between responsive fragments and gene expression changes, including Wnt/p53 targets after ATF2 or LEF1 depletion. A deep learning model recapitulates enhancer grammar, including cooperative motif syntax and flanking sequence context. Applying this framework to 16p12.1 deletion identifies responsive fragments associated with genes involved in neuronal function, providing a scalable readout of enhancer dynamics across genetic perturbations.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118131"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179528","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

Untranslated region rewiring defines a novel class of oncogene fusions. 非翻译区重新布线定义了一类新的癌基因融合。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118145

Marina Cerqua, Estelle Bigot, Cédric Chaveroux, Paolo M Comoglio, Dogus M Altintas

{"title":"Untranslated region rewiring defines a novel class of oncogene fusions.","authors":"Marina Cerqua, Estelle Bigot, Cédric Chaveroux, Paolo M Comoglio, Dogus M Altintas","doi":"10.1016/j.celrep.2026.118145","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118145","url":null,"abstract":"Gene fusions in cancer are traditionally understood to generate hybrid proteins with altered functions that promote malignancy. Here, we define a previously unrecognized class of oncogenic fusions that preserve protein structure but replace the 5' untranslated region (5' UTR), thereby rewiring translational regulation. Using the MET oncogene as a paradigm, we show that 5' UTR-replacing fusions, identified across >200,000 cancer samples, increase MET protein abundance 5- to 10-fold without corresponding changes in mRNA levels. The resulting receptor remains correctly localized, ligand-responsive, and active, thereby promoting cell survival and motility. These fusion transcripts are detected following irradiation, documenting UTR rewiring in a post-treatment context. Beyond MET, similar 5' UTR-replacing fusions occur in FGFR1, JAK2, and NTRK2, where partner-derived 5 'UTRs are associated with reduced regulatory complexity and enhanced protein output. Together, our findings establish UTR rewiring as an overlooked mechanism of oncogene overexpression with implications for cancer genome annotation and precision oncology.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118145"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179574","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

Spatial distribution of blood-brain barrier membrane proteins is controlled by sorting motifs and physiological signals in vivo. 血脑屏障膜蛋白的空间分布受体内分选基序和生理信号的控制。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118134

Joseph Amick, Shamika Bhandarkar, Douglas R Wilcox, Solenn Boloker, Yi Daniel Lu, Chenghua Gu

{"title":"Spatial distribution of blood-brain barrier membrane proteins is controlled by sorting motifs and physiological signals in vivo.","authors":"Joseph Amick, Shamika Bhandarkar, Douglas R Wilcox, Solenn Boloker, Yi Daniel Lu, Chenghua Gu","doi":"10.1016/j.celrep.2026.118134","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118134","url":null,"abstract":"The blood-brain barrier (BBB), formed by brain endothelial cells (BECs), creates a safe and homeostatic environment for proper brain function. While BECs are extraordinarily thin, their luminal and abluminal plasma membranes face markedly different environments: the blood and brain parenchyma, respectively. How BBB membrane proteins are spatially distributed between these membranes and the factors regulating their localization are not clear. Here, we establish a method for measuring polarized protein sorting at the BBB in vivo. We characterize the distribution of transporters and receptors on the luminal and abluminal plasma membranes and identify protein-intrinsic motifs that control polarized sorting. Finally, we observe a change in membrane protein distribution that aligns with circadian rhythms, revealing an under-appreciated dimension of BBB dynamics. This method can be broadly used for evaluating membrane protein landscape changes during development and disease and for choosing optimal molecular targets for BBB-crossing therapeutics.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118134"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179551","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

Cingulate thrombospondin 4 protects against neuropathic pain and comorbid anxiodepression via interaction with EAAT2. 扣带血栓反应蛋白4通过与EAAT2的相互作用预防神经性疼痛和共病性焦虑抑郁。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118112

Wan-Neng Liu, Wen-Juan Han, Zhi-Wei Dou, Ke-Xin Liu, Rui Zhao, Rou-Gang Xie, Sheng-Xi Wu, Zhen-Zhen Li, Ceng Luo

{"title":"Cingulate thrombospondin 4 protects against neuropathic pain and comorbid anxiodepression via interaction with EAAT2.","authors":"Wan-Neng Liu, Wen-Juan Han, Zhi-Wei Dou, Ke-Xin Liu, Rui Zhao, Rou-Gang Xie, Sheng-Xi Wu, Zhen-Zhen Li, Ceng Luo","doi":"10.1016/j.celrep.2026.118112","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118112","url":null,"abstract":"Patients with neuropathic pain frequently present with emotional disorders. Cellular plasticity within anterior cingulate cortex (ACC) is considered as a key interface linking pain and emotion. However, mounting efforts have been devoted to elucidating intracellular mechanisms of plasticity, how extracellular alterations trigger intracellular changes remains elusive. Thrombospondin (THBS), a key component of extracellular matrix (ECM), is involved in various pathophysiological processes. Here, we show that THBS4 is downregulated in the ACC following peripheral neuropathy. Overexpressing cingulate THBS4 alleviates pain hypersensitivity and anxiodepression. Mechanistic analysis indicates that THBS4 maintains glutamate homeostasis via direct regulation of excitatory amino acid transporter 2 (EAAT2) in astrocytic membrane, further stabilizing abnormal plasticity of pyramidal neurons and eventually producing analgesic, anxiolytic, and antidepressive effects. Taken together, we show THBS4-mediated neuron-astrocyte crosstalk as a key mechanism underlying neuropathic pain and comorbid anxiodepression. Recombinant THBS4 protein represents a promising therapeutic strategy for treatment of neuropathic pain and anxiodepression.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118112"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179426","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

USP9X promotes the degradation of trapped translation factors on collided ribosomes. USP9X促进碰撞核糖体上被困翻译因子的降解。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118125

Wojciech Teodorowicz, Lukas-Adrian Gurzeler, Oliver Mühlemann

{"title":"USP9X promotes the degradation of trapped translation factors on collided ribosomes.","authors":"Wojciech Teodorowicz, Lukas-Adrian Gurzeler, Oliver Mühlemann","doi":"10.1016/j.celrep.2026.118125","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.118125","url":null,"abstract":"Various ribosome-associated quality control pathways safeguard translation fidelity by detecting and resolving aberrant translation events. Recently, a pathway that senses stalled ribosomes with an occluded A-site has been described. The small molecules NVS1.1 and ternatin-4 induce ribosome stalling by trapping eukaryotic release factor 1 (eRF1) and elongation factor 1A1 (eEF1A1), respectively, within the ribosomal A-site, thereby promoting their ubiquitination and proteasomal degradation. Additionally to the previously identified factors GCN1, RNF14, and RNF25, we identify here the deubiquitinase USP9X as a regulator of this pathway. In the absence of USP9X deubiquitinase activity, eRF1 is still ubiquitinated but fails to undergo efficient degradation. However, compared with wild-type cells, K6-linked ubiquitin chains accumulate on eRF1 in cells lacking USP9X activity, suggesting that USP9X trims K6-linked ubiquitin chains during a late step of substrate processing. Furthermore, clearance of trapped eRF1 engages a feedback mechanism involving 4EHP and the integrated stress response (ISR) to suppress translation, whereas impaired degradation prevents translational shutdown.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 10","pages":"118125"},"PeriodicalIF":7.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179586","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

Proprioceptive sensory-driven mechanisms shape Clarke's column development. 本体感受的丰富性非常在意形状克拉克列的发展机制。

IF 7.7 1区生物学

Cell reports Pub Date : 2026-10-13 DOI: 10.1016/j.celrep.2026.118160

Injun Song, Junhee Park, Tery Yun, Yurim Seong, Han Kyoung Choe, Myungin Baek

引用次数: 0