Cell reports最新文献_第4页

GLIS3 marks a neural-like progenitor cell state that drives metastasis in pancreatic ductal adenocarcinoma. GLIS3标志着驱动胰腺导管腺癌转移的神经样祖细胞状态。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-27 DOI: 10.1016/j.celrep.2026.117314

Dennis Gong, Jimmy A Guo, Jennifer Su, Sueda Cetinkaya, Connor Hennessey, Patrick Yu, Ananya Jambhale, Peter L Wang, Nicholas J Caldwell, Ashley Lam, Junning Wang, Carina Shiau, Kevin S Kapner, Julien Dilly, Laleh Abbassi, Seema Chugh, Shatavisha Dasgupta, Jonathan Nowak, Brian M Wolpin, M Lisa Zhang, Mari Mino-Kenudson, Tyler Jacks, Andrew J Aguirre, William L Hwang

{"title":"GLIS3 marks a neural-like progenitor cell state that drives metastasis in pancreatic ductal adenocarcinoma.","authors":"Dennis Gong, Jimmy A Guo, Jennifer Su, Sueda Cetinkaya, Connor Hennessey, Patrick Yu, Ananya Jambhale, Peter L Wang, Nicholas J Caldwell, Ashley Lam, Junning Wang, Carina Shiau, Kevin S Kapner, Julien Dilly, Laleh Abbassi, Seema Chugh, Shatavisha Dasgupta, Jonathan Nowak, Brian M Wolpin, M Lisa Zhang, Mari Mino-Kenudson, Tyler Jacks, Andrew J Aguirre, William L Hwang","doi":"10.1016/j.celrep.2026.117314","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117314","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) frequently recurs and metastasizes despite intensive therapy. The neural-like progenitor (NRP) transcriptional program is enriched in residual disease after neoadjuvant chemotherapy and radiotherapy, but its basis has remained unclear. We hypothesized that NRP represents a regeneration program co-opted by tumors recovering from cytotoxic injury. NRP signatures were strongly enriched in normal pancreatic injury and regeneration, and NRP cancer cells co-expressed transcription factors involved in pancreatic development. Our data support cell-intrinsic contributions and implicate IL-1β-associated inflammatory signaling as a plausible microenvironmental driver of elevated NRP expression. To enable direct phenotypic comparison with other cancer cell states, we established isogenic mouse organoid overexpression models for transcription factors linked to NRP, classical, and basal-like states. Glis3 emerged as a key NRP-associated factor, promoting clonogenicity, tumor growth, and metastasis. These findings identify a clinically relevant developmental regeneration program that emerges in PDAC after treatment.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 5","pages":"117314"},"PeriodicalIF":6.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763762","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

SEPHS2 loss reprograms cancer metabolism from oxidative phosphorylation to gluconeogenesis via PCK1 stabilization. SEPHS2缺失通过PCK1稳定将癌症代谢从氧化磷酸化重编程为糖异生。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-25 DOI: 10.1016/j.celrep.2026.117297

Yihuizhi Zhang, Qinghua Zhang, Bi Wei, Wenzhou Wang, Xinyu Chen, Weijian Ding, Chenguang Li, Yirui Ye, Jiali Xu, Weibo Zhang, Linyue Li, Fengyi Mai, Wenyou He, Xiancai Du, Keyu Zhao, Zining Zhao, Jingnan Huang, Yuchun Niu, Yue Zhang, Lingyun Dai, Baotong Zhang, Siyuan Xia

{"title":"SEPHS2 loss reprograms cancer metabolism from oxidative phosphorylation to gluconeogenesis via PCK1 stabilization.","authors":"Yihuizhi Zhang, Qinghua Zhang, Bi Wei, Wenzhou Wang, Xinyu Chen, Weijian Ding, Chenguang Li, Yirui Ye, Jiali Xu, Weibo Zhang, Linyue Li, Fengyi Mai, Wenyou He, Xiancai Du, Keyu Zhao, Zining Zhao, Jingnan Huang, Yuchun Niu, Yue Zhang, Lingyun Dai, Baotong Zhang, Siyuan Xia","doi":"10.1016/j.celrep.2026.117297","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117297","url":null,"abstract":"Selenium maintains cellular redox homeostasis primarily through its incorporation into selenoproteins. However, whether and how selenium metabolism modulates oxidative phosphorylation (OXPHOS), a major endogenous source of oxidative stress, has remained unclear. Here, we performed an OXPHOS-focused screen targeting selenium-metabolizing enzymes and identified SEPHS2 as a central hub linking selenium metabolism to OXPHOS. SEPHS2 knockout suppresses OXPHOS while retaining glucose as the primary carbon source of cellular respiration and redirecting glucose metabolism toward gluconeogenesis and the downstream pentose phosphate pathway (PPP). Mechanistically, SEPHS2 loss elevates intracellular NAD+ levels, thereby activating the deacetylase SIRT2 as a cofactor and promoting deacetylation-dependent stabilization of the gluconeogenic enzyme PCK1. Under selenium-limited conditions, SEPHS2 is reduced. SEPHS2 loss promotes tumor spread to the lung and sensitizes tumors to the PPP inhibitor 6-aminonicotinamide. These findings define a selenoprotein biosynthesis-independent role of SEPHS2 in regulating OXPHOS and unveil the PPP as a therapeutic vulnerability in tumors adapting to a selenium-limited microenvironment.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 5","pages":"117297"},"PeriodicalIF":6.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763677","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

Ubiquilin1 restricts influenza viral replication through trapping vRNP in the late endosomes. 泛素1通过在后期核内体中捕获vRNP来限制流感病毒的复制。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-25 DOI: 10.1016/j.celrep.2026.117310

Bi-Rong Zheng, Zhaohuan Wang, Wei Ran, Jiafan Miao, Shu-Rui Liu, Yu Ye, Keda Shi, Miao He, Junwei Li, Hui Zhang, Jin-Cun Zhao, Chun-Mei Li, Deyin Guo, Panpan Hou

{"title":"Ubiquilin1 restricts influenza viral replication through trapping vRNP in the late endosomes.","authors":"Bi-Rong Zheng, Zhaohuan Wang, Wei Ran, Jiafan Miao, Shu-Rui Liu, Yu Ye, Keda Shi, Miao He, Junwei Li, Hui Zhang, Jin-Cun Zhao, Chun-Mei Li, Deyin Guo, Panpan Hou","doi":"10.1016/j.celrep.2026.117310","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117310","url":null,"abstract":"Influenza A viruses (IAVs) cause seasonal epidemics and occasional pandemics in humans. Although multiple stages of the viral life cycle have been well characterized, the molecular mechanisms governing viral uncoating remain incompletely understood. Here, we identify the host protein Ubiquilin1 (UBQLN1) as a restriction factor that inhibits IAV uncoating. UBQLN1 interacts with viral ribonucleoproteins (vRNPs), preventing HDAC6-dependent uncoating and sequestering vRNPs in late endosomes. In addition, UBQLN1 disrupts the interaction between vRNPs and importins, thereby impairing nuclear import of vRNPs. Functionally, UBQLN1 restricts replication of multiple influenza virus strains both in vitro and in vivo. UBQLN1 knockout increases cellular susceptibility to infection and promotes viral replication, and loss of Ubqln1 in mice leads to higher viral loads and exacerbated disease severity. These findings identify UBQLN1 as a host factor that blocks influenza infection by targeting viral uncoating and suggest a potential antiviral strategy.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 5","pages":"117310"},"PeriodicalIF":6.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763747","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

Multiple roads to IgE memory: A pluralistic model of IgE immunity. IgE记忆的多种途径：IgE免疫的多元模型。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-25 DOI: 10.1016/j.celrep.2026.117312

Shweta Chaudhary, Shivangi Dave, André Ballesteros-Tato

引用次数: 0

Powering next-generation precision therapeutics through integrated synthetic transcriptional systems. 通过集成的合成转录系统为下一代精确治疗提供动力。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-24 DOI: 10.1016/j.celrep.2026.117308

Bei Zhong, Li Zhou, Rongqi Li, Hui Wang, Wei Li, Fei Teng

{"title":"Powering next-generation precision therapeutics through integrated synthetic transcriptional systems.","authors":"Bei Zhong, Li Zhou, Rongqi Li, Hui Wang, Wei Li, Fei Teng","doi":"10.1016/j.celrep.2026.117308","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117308","url":null,"abstract":"Mammalian synthetic biology holds great promise for treating complex diseases but faces challenges such as functional leakage and imprecise control dynamics. The advent of synthetic promoters (synPs) and transcription factors (synTFs) has expanded the genetic toolkit, and their coordinated integration enables precise, intelligent, and multidimensional regulation. Advances in promoter engineering and modular synTF design, aided by artificial intelligence, have shifted the field from empirical, trial-and-error discovery to rational, predictive design. This progress has facilitated the construction of synthetic circuits that integrate multiple endogenous and exogenous inputs through logic gates, feedback loops, and tunable systems. Such innovations support dynamic, spatiotemporally precise control, enhancing therapeutic precision and reducing off-target effects. By addressing key translational requirements, including multi-input sensing, tunable expression, and high orthogonality, integrated synP-synTF systems are advancing sophisticated mammalian therapeutics. This review summarizes progress in engineered and integrated systems, highlighting dynamic regulatory strategies and their therapeutic applications.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 5","pages":"117308"},"PeriodicalIF":6.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763562","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

Radial astroglia cooperate with microglia to clear neuronal cell bodies during zebrafish optic tectum development. 斑马鱼视顶盖发育过程中星形胶质细胞与小胶质细胞协同清除神经元细胞体。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-24 DOI: 10.1016/j.celrep.2026.117345

Heather M Barber, Cassidy G Robbins, Zachary Cutler, Robin I Brown, Lauren E Jung, Inge Werkman, Sarah Kucenas

引用次数: 0

Complement C3aR deletion does not attenuate degeneration in a tauopathy model or alter acute inflammation-induced gene expression changes. 补体C3aR缺失不会减轻牛头病变模型中的变性或改变急性炎症诱导的基因表达变化。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-24 DOI: 10.1016/j.celrep.2026.117313

Yuanyuan Wang, Shristi Pandey, Martin Weber, Man Kin Choy, Tiffany Wu, Tania Chernov-Rogan, Max Adrian, Ming-Chi Tsai, Hai Ngu, Oded Foreman, Luke Xie, Jesse E Hanson

{"title":"Complement C3aR deletion does not attenuate degeneration in a tauopathy model or alter acute inflammation-induced gene expression changes.","authors":"Yuanyuan Wang, Shristi Pandey, Martin Weber, Man Kin Choy, Tiffany Wu, Tania Chernov-Rogan, Max Adrian, Ming-Chi Tsai, Hai Ngu, Oded Foreman, Luke Xie, Jesse E Hanson","doi":"10.1016/j.celrep.2026.117313","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117313","url":null,"abstract":"Aberrant activation of the classical complement pathway in the brain is implicated in contributing to synapse loss and neurodegeneration in various neurodegenerative conditions. Given that C3aR is a druggable target in the complement pathway, we evaluated the potential of C3aR knockout (KO) to rescue neurodegeneration in a tauopathy model and neuroinflammatory responses in an acute endotoxemia model. We found that C3aR KO did not rescue Tau pathology, microglia activation markers, neurodegeneration, or behavioral abnormalities in tauopathy model mice. While we found that endotoxemia resulted in numerous transcriptional changes, including distinct alterations in subpopulations of microglia, astrocytes, and oligodendrocytes, C3aR KO did not impact these alterations. Together, our results suggest that the beneficial effects of blocking the complement classical pathway in neurodegeneration models are likely independent of C3aR activation and raise questions about the rationale for therapeutically targeting C3aR for neurodegenerative disease.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 5","pages":"117313"},"PeriodicalIF":6.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763778","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

SFPQ prevents MDA5-mediated activation of innate immunity and preserves cell viability. SFPQ阻止mda5介导的先天免疫激活并保持细胞活力。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-24 DOI: 10.1016/j.celrep.2026.117291

Huirong Zhang, Runjie Yuan, Praneet K Sandhu, Justin T Landis, Dirk P Dittmer, Blossom Damania

{"title":"SFPQ prevents MDA5-mediated activation of innate immunity and preserves cell viability.","authors":"Huirong Zhang, Runjie Yuan, Praneet K Sandhu, Justin T Landis, Dirk P Dittmer, Blossom Damania","doi":"10.1016/j.celrep.2026.117291","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117291","url":null,"abstract":"The melanoma differentiation-associated gene 5 (MDA5) sensor recognizes double-stranded RNA (dsRNA) produced during viral infections, leading to type I interferon (IFN) production. Host proteins can shield endogenous dsRNA from MDA5 through RNA modifications, such as A-to-I editing of dsRNA by adenosine deaminase acting on RNA 1 (ADAR1). The splicing factor proline- and glutamine-rich (SFPQ) is an RNA-binding protein that regulates RNA biogenesis. However, its role in innate immunity has not been previously explored. We report that SFPQ can promote viral replication of Kaposi's sarcoma-associated herpesvirus (KSHV) and demonstrate that SFPQ can prevent IFN production not only in the context of viral replication but also in uninfected cells. Furthermore, SFPQ associates with ADAR1 and modulates A-to-I editing of cellular RNA transcripts. Moreover, SFPQ depletion in uninfected cells induced IFN response genes, including MDA5 and ZBP1, and impaired cell growth. In summary, SFPQ binds ADAR1 and modulates its editing function, thereby preventing cellular RNAs from activating MDA5-mediated innate immune responses.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 5","pages":"117291"},"PeriodicalIF":6.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763669","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

Conjugated pneumococcal vaccination yields broadly functional, mucosal-directed responses detectable up to at least 42 months in older adults. 结合肺炎球菌疫苗产生广泛的功能，粘膜导向的反应，可检测到至少42个月的老年人。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-24 DOI: 10.1016/j.celrep.2026.117307

Qixin Wang, Ross Blanc, Kate S Levine, Hadar Malca, Lindsay R Grant, Ashley Miller, Jelena Vojicic, Galit Alter, Bradford D Gessner, Ryan P McNamara

{"title":"Conjugated pneumococcal vaccination yields broadly functional, mucosal-directed responses detectable up to at least 42 months in older adults.","authors":"Qixin Wang, Ross Blanc, Kate S Levine, Hadar Malca, Lindsay R Grant, Ashley Miller, Jelena Vojicic, Galit Alter, Bradford D Gessner, Ryan P McNamara","doi":"10.1016/j.celrep.2026.117307","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117307","url":null,"abstract":"Streptococcus pneumoniae is a causative agent of severe pneumonia, particularly in at-risk populations. To characterize immune responses elicited by the 13-valent pneumococcal conjugate (PCV13) or 23-valent pneumococcal polysaccharide (PPSV23) vaccines, we deeply profiled antibody responses against select serotypes (Pn1, Pn3, Pn6A, Pn6B, Pn7F, Pn19A, Pn19F, and Pn23F) at 1, 12, and 42 months post-vaccination in vaccine-naive adults aged 60-64 years. At 1 month post-vaccination, recipients of PCV13 had higher IgG, IgA, and antibody-dependent complement deposition (ADCD) levels than PPSV23 recipients, particularly against serotype Pn6A. At 12 months post-vaccination, PCV13 induced IgA and IgG-ADCD networks against S. pneumoniae Pn1, Pn6A, Pn6B, and Pn7F, while only serotype Pn6A was targeted by both mechanisms in PPSV23 recipients. At 42 months post-vaccination, recipients of PCV13 retained IgA and IgG-ADCD networks against multiple S. pneumoniae serotypes. A durable IgA- and ADCD-primed response in PCV13 recipients points to a strong, multifunctional humoral response by this vaccine platform.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 5","pages":"117307"},"PeriodicalIF":6.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763810","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

Spatially local inhibition and synaptic plasticity together enable dynamic, context-dependent integration of parallel sensory pathways. 空间局部抑制和突触可塑性共同使平行感觉通路的动态、情境依赖的整合成为可能。

IF 6.9 1区生物学

Cell reports Pub Date : 2026-04-24 DOI: 10.1016/j.celrep.2026.117306

Qiang Chen, Fred Rieke

{"title":"Spatially local inhibition and synaptic plasticity together enable dynamic, context-dependent integration of parallel sensory pathways.","authors":"Qiang Chen, Fred Rieke","doi":"10.1016/j.celrep.2026.117306","DOIUrl":"https://doi.org/10.1016/j.celrep.2026.117306","url":null,"abstract":"Retinal ganglion cells have traditionally been grouped into cells that are sensitive to luminance but not spatial structure and cells with responses that are enhanced by spatial structure. Neither category describes mouse Off-transient alpha cells, which respond strongly to spatially homogeneous inputs and are suppressed by spatial structure. We identified two circuit mechanisms that together can explain this unusual spatial selectivity. First, the inhibition that controls responses of these cells is tuned to finer spatial structure than excitation, causing the balance of excitation and inhibition to depend on spatial scale. Second, the excitatory synapses onto these cells undergo strong synaptic depression, and the modulation of that depression by presynaptic inhibition amplifies responses to the transition from spatially structured to homogeneous inputs. A spatiotemporal computational model incorporating these circuit features quantitatively recapitulates the observed responses. These findings reveal how localized inhibition and short-term plasticity jointly create the distinctive spatial selectivity of Off-transient cells.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 5","pages":"117306"},"PeriodicalIF":6.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763705","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