Cell reports最新文献_第3页

A bacterial expression cloning screen reveals single-stranded DNA-binding proteins as potent desicco-protectants. 细菌表达克隆筛选发现单链 DNA 结合蛋白是有效的脱盐保护剂。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-11 DOI: 10.1016/j.celrep.2024.114956

Jonathan D Hibshman, Courtney M Clark-Hachtel, Kerry S Bloom, Bob Goldstein

{"title":"A bacterial expression cloning screen reveals single-stranded DNA-binding proteins as potent desicco-protectants.","authors":"Jonathan D Hibshman, Courtney M Clark-Hachtel, Kerry S Bloom, Bob Goldstein","doi":"10.1016/j.celrep.2024.114956","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114956","url":null,"abstract":"Desiccation kills most cells. Some proteins have been identified to help certain cells survive desiccation, but many protein protectants are likely to be unknown. Moreover, the mechanisms ensuring protection of key cellular components are incompletely understood. We devised an expression-cloning approach to discover further protectants. We expressed cDNA libraries from two species of tardigrades in E. coli, and we subjected the bacteria to desiccation to select for survivors. Sequencing the populations of surviving bacteria revealed enrichment of mitochondrial single-stranded DNA-binding proteins (mtSSBs) from both tardigrade species. Expression of mtSSBs in bacteria improved desiccation survival as strongly as the best tardigrade protectants known to date. We found that DNA-binding activity of mtSSBs was necessary and sufficient to improve the desiccation tolerance of bacteria. Although tardigrade mtSSBs were among the strongest protectants we found, single-stranded DNA binding proteins in general offered some protection. These results identify single-stranded DNA-binding proteins as potent desicco-protectants.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114956"},"PeriodicalIF":7.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615862","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 platform of functional studies of ESCC-associated gene mutations identifies the roles of TGFBR2 in ESCC progression and metastasis. ESCC 相关基因突变的功能研究平台确定了 TGFBR2 在 ESCC 进展和转移中的作用。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-10 DOI: 10.1016/j.celrep.2024.114952

Jian Wang, Jiajia Du, Xiangmeng Luo, Linjie Guo, Yixin Liu, Jianfeng Zhou, Yang Zou, Zhenghao Lu, Xiangyu Pan, Xuelan Chen, Ailing Zhong, Xudong Wan, Lu Wang, Hongyu Liu, Siqi Dai, Shiyu Zhang, Xingyu Xiong, Ping Tan, Manli Wang, Baohong Wu, Qi Zhang, Yingjie Wang, Mengsha Zhang, Runda Lu, Huahang Lin, Yuan Li, Yaxin Li, Zongkai Han, Longqi Chen, Bing Hu, Yu Liu, Feifei Na, Chong Chen

{"title":"A platform of functional studies of ESCC-associated gene mutations identifies the roles of TGFBR2 in ESCC progression and metastasis.","authors":"Jian Wang, Jiajia Du, Xiangmeng Luo, Linjie Guo, Yixin Liu, Jianfeng Zhou, Yang Zou, Zhenghao Lu, Xiangyu Pan, Xuelan Chen, Ailing Zhong, Xudong Wan, Lu Wang, Hongyu Liu, Siqi Dai, Shiyu Zhang, Xingyu Xiong, Ping Tan, Manli Wang, Baohong Wu, Qi Zhang, Yingjie Wang, Mengsha Zhang, Runda Lu, Huahang Lin, Yuan Li, Yaxin Li, Zongkai Han, Longqi Chen, Bing Hu, Yu Liu, Feifei Na, Chong Chen","doi":"10.1016/j.celrep.2024.114952","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114952","url":null,"abstract":"Genomics studies have detected numerous genetic alterations in esophageal squamous cell carcinoma (ESCC). However, the functions of these mutations largely remain elusive, partially due to a lack of feasible animal models. Here, we report a convenient platform with CRISPR-Cas9-mediated introduction of genetic alterations and orthotopic transplantation to generate a series of primary ESCC models in mice. With this platform, we validate multiple frequently mutated genes, including EP300, FAT1/2/4, KMT2D, NOTCH2, and TGFBR2, as tumor-suppressor genes in ESCC. Among them, TGFBR2 loss dramatically promotes tumorigenesis and multi-organ metastasis. Paradoxically, TGFBR2 deficiency leads to Smad3 activation, and disruption of Smad3 partially restrains the progression of Tgfbr2-mutated tumors. Drug screening with tumor organoids identifies that pinaverium bromide represses Smad3 activity and restrains Tgfbr2-deficient ESCC. Our studies provide a highly efficient platform to investigate the in vivo functions of ESCC-associated mutations and develop potential treatments for this miserable malignancy.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114952"},"PeriodicalIF":7.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615904","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

Domestication-selected COG4-OsbZIP23 module regulates chilling tolerance in rice. 驯化选择的 COG4-OsbZIP23 模块调控水稻的耐寒性。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-10 DOI: 10.1016/j.celrep.2024.114965

Shenli Sun, Dongfeng Liu, Wei Luo, Zhitao Li, Jinglei Feng, Yalong Guo, Kang Chong, Yunyuan Xu

{"title":"Domestication-selected COG4-OsbZIP23 module regulates chilling tolerance in rice.","authors":"Shenli Sun, Dongfeng Liu, Wei Luo, Zhitao Li, Jinglei Feng, Yalong Guo, Kang Chong, Yunyuan Xu","doi":"10.1016/j.celrep.2024.114965","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114965","url":null,"abstract":"Identifying excellent natural variations is the foundation for breeding. Several major genes of quantitative trait loci for chilling tolerance at the seedling stage (qCTS) have been identified. However, less is known about the dual elite modules for the tolerance. Here, we report the major gene of qCTS1-2, Chilling-tolerance in Geng/japonica rice 4 (COG4), encoding the transcription factor ENAC1, coupled with OsbZIP23 to positively regulate chilling tolerance. The haplotype analysis and geographical distribution show that most of the chilling-tolerant japonica varieties carry Var9(CT) at -317 in COG4 (COG4jap). The COG4jap promoter is preferentially bound by cold-induced OsbZIP23 to cause a higher expression of COG4jap compared to COG4ind, which promotes multiple pathways for the tolerance. Both COG4jap and OsbZIP23jap are artificially selected and retained in japonica varieties during domestication. These results not only reveal the regulatory mechanism of OsbZIP23jap-COG4jap module but also provide valuable variations for molecular design breeding.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114965"},"PeriodicalIF":7.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615882","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

Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus. 红斑狼疮患者生殖中心 B 细胞的分区循环异常会影响适当的选择。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-10 DOI: 10.1016/j.celrep.2024.114978

Gina M Sanchez, Eden S Hirsch, Arthur VanValkenburg, Daniel P Mayer, Komi Gbedande, Rebecca L Francis, Wenzhi Song, Olivia Q Antao, Kyleigh E Brimmer, Alexander Lemenze, Robin Stephens, W Evan Johnson, Jason S Weinstein

{"title":"Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus.","authors":"Gina M Sanchez, Eden S Hirsch, Arthur VanValkenburg, Daniel P Mayer, Komi Gbedande, Rebecca L Francis, Wenzhi Song, Olivia Q Antao, Kyleigh E Brimmer, Alexander Lemenze, Robin Stephens, W Evan Johnson, Jason S Weinstein","doi":"10.1016/j.celrep.2024.114978","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114978","url":null,"abstract":"Autoimmune diseases such as lupus are characterized by polyclonal B cell activation, leading to the production of autoantibodies. The mechanism leading to B cell dysregulation is unclear; however, the defect may lie in selection within germinal centers (GCs). GC B cells cycle between proliferation and mutation in the dark zone and selection in the light zone (LZ). Temporal assessment of GCs from mice with either persistent infection or lupus showed an accumulation of LZ B cells. Yet, only in lupus, GC B cells exhibited reduced proliferation and progressive loss of MYC and FOXO1, which regulate zonal recycling and differentiation. As lupus progressed, decreased mutational frequency and repertoire diversity were associated with reduced responsiveness to CD40 signaling, despite accumulation of plasma cells. Collectively, these findings suggest that lupus disease progression coincides with an intrinsic defect in LZ B cell signaling, altering the zonal recycling, selection, and differentiation of autoreactive B cells.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114978"},"PeriodicalIF":7.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615913","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

Metabolic disruption exacerbates intestinal damage during sleep deprivation by abolishing HIF1α-mediated repair. 代谢紊乱通过取消 HIF1α 介导的修复，加剧了睡眠剥夺期间的肠道损伤。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-10 DOI: 10.1016/j.celrep.2024.114915

Hai-Yi Zhang, Ya-Qing Shu, Yan Li, Ya-Lin Hu, Zhi-Hong Wu, Zhi-Peng Li, Yao Deng, Zi-Jian Zheng, Xiao-Jing Zhang, Liu-Fei Gong, Yang Luo, Xiao-Yu Wang, Hong-Ping Li, Xiao-Ping Liao, Gong Li, Hao Ren, Wei Qiu, Jian Sun

引用次数: 0

ZDHHC3-mediated SCAP S-acylation promotes cholesterol biosynthesis and tumor immune escape in hepatocellular carcinoma. ZDHHC3 介导的 SCAP S-acylation 促进肝细胞癌中胆固醇的生物合成和肿瘤免疫逃逸。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-09 DOI: 10.1016/j.celrep.2024.114962

Mingzhi Wu, Xiaojun Zhou, Xinyi Zhou, Genxin Wang, Yiqun Zeng, Jun Li, Edward V Prochownik, Fubing Wang, Youjun Li

{"title":"ZDHHC3-mediated SCAP S-acylation promotes cholesterol biosynthesis and tumor immune escape in hepatocellular carcinoma.","authors":"Mingzhi Wu, Xiaojun Zhou, Xinyi Zhou, Genxin Wang, Yiqun Zeng, Jun Li, Edward V Prochownik, Fubing Wang, Youjun Li","doi":"10.1016/j.celrep.2024.114962","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114962","url":null,"abstract":"Cholesterol metabolism reprogramming plays essential roles in hepatocellular carcinoma (HCC). However, precisely how cholesterol metabolism is dysregulated is not clear. Here, we show that the palmitoyltransferase ZDHHC3 and depalmitoylase ABHD17A regulate HCC cell cholesterol biosynthesis by dynamically S-acylating SREBP cleavage-activating protein (SCAP). SCAP S-acylation by ZDHHC3 at C264 antagonizes HACE1-mediated SCAP ubiquitination. Intriguingly, SREBP2 transcriptionally upregulates ZDHHC3 to form a positive feedback loop, which explains why negative feedback regulation of SCAP/SREBP2 signaling fails in HCC. Increased cholesterol in the tumor microenvironment (TME) restrains CD4+ T cell cytotoxicity. Hence, the cholesterol metabolism reprogramming and cholesterol level alternation in the TME cooperate to promote HCC development. We identified a small-molecule inhibitor of ZDHHC3 that, combined with anti-PD-1 immunotherapy, inhibited diethyl nitrosamine (DEN)/CCl4-induced HCC growth in mice. ZDHHC3-mediated SCAP S-acylation reprograms cholesterol metabolism and promotes HCC immune escape. ZDHHC3 is thus identified as a rational chemotherapy target for HCC.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114962"},"PeriodicalIF":7.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615397","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

Residue Y362 is crucial for FLIP_L to impart catalytic activity to pro-caspase-8 to suppress necroptosis. Y362残基对于FLIPL赋予原-caspase-8催化活性以抑制坏死至关重要。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-08 DOI: 10.1016/j.celrep.2024.114966

Mao Hong, Xiurong Wu, Peng He, Rangxin Peng, Lang Li, Su-Qin Wu, Jianbang Zhao, Aidong Han, Yingying Zhang, Jiahuai Han, Zhang-Hua Yang

{"title":"Residue Y362 is crucial for FLIPL to impart catalytic activity to pro-caspase-8 to suppress necroptosis.","authors":"Mao Hong, Xiurong Wu, Peng He, Rangxin Peng, Lang Li, Su-Qin Wu, Jianbang Zhao, Aidong Han, Yingying Zhang, Jiahuai Han, Zhang-Hua Yang","doi":"10.1016/j.celrep.2024.114966","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114966","url":null,"abstract":"The pro-form of caspase-8 prevents necroptosis by functioning in a proteolytically active complex with its catalytic-dead homolog, FLICE (FADD [Fas-associated death domain]-like interleukin 1β-converting enzyme)-like inhibitory protein long-form (FLIPL). However, how FLIPL imparts caspase-8 the catalytic activity to suppress necroptosis remains elusive. Here, we show that the protease-like domain of FLIPL is essential for the activity of the caspase-8-FLIPL heterodimer in blocking necroptosis. While substitution of two amino acids whose difference may contribute to the pseudo-caspase property of FLIPL with the corresponding amino acids in caspase-8 does not restore the protease activity of FLIPL, one of the amino acid replacements, tyrosine (Y) 362 to cysteine (C), is sufficient to completely abolish the activity of the caspase-8-FLIPL heterodimer in cleaving receptor-interacting protein 1 (RIP1), thus releasing the necroptosis blockade. Unconstrained necroptosis is observed in embryonic day (E)10.5-E11.5 embryos of FLIPL-Y362C knockin mice. Collectively, these results reveal that the protease-like domain of FLIPL has a special structure that imparts the pro-caspase-8-FLIPL heterodimer a unique catalytic activity toward RIP1 to prevent necroptosis.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114966"},"PeriodicalIF":7.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615231","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

TCR-mimicking STAR conveys superior sensitivity over CAR in targeting tumors with low-density neoantigens. 在靶向具有低密度新抗原的肿瘤方面，TCR 模仿 STAR 比 CAR 具有更高的灵敏度。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-08 DOI: 10.1016/j.celrep.2024.114949

Daosheng Huang, Yi Li, Wei Rui, Keyong Sun, Zhixiao Zhou, Xiachen Lv, Li Yu, Junfan Chen, Jing Zhou, Vincent Liu, Jiasheng Wang, Xun Lan, Yang-Xin Fu, Xueqiang Zhao, Xin Lin

{"title":"TCR-mimicking STAR conveys superior sensitivity over CAR in targeting tumors with low-density neoantigens.","authors":"Daosheng Huang, Yi Li, Wei Rui, Keyong Sun, Zhixiao Zhou, Xiachen Lv, Li Yu, Junfan Chen, Jing Zhou, Vincent Liu, Jiasheng Wang, Xun Lan, Yang-Xin Fu, Xueqiang Zhao, Xin Lin","doi":"10.1016/j.celrep.2024.114949","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114949","url":null,"abstract":"Targeting tumor-specific neoantigens holds promise for cancer immunotherapy, but their ultra-low expression on tumor cells poses challenges for T cell therapies. Here, we found that chimeric antigen receptors (CARs) exhibit 10-100 times lower sensitivity than T cell receptors (TCRs) when targeting human leukocyte antigen (HLA) class I-presented p53R175H neoantigen. To enhance CAR functionality, we introduced T cell receptor fusion constructs (TRuCs) and synthetic TCRs and antigen receptors (STARs). Our data show that STARs optimally reproduce TCR antigen sensitivity, outperforming CARs and TRuCs in redirecting CD8+ and CD4+ T cells to recognize HLA class I neoantigens. STAR-T cells demonstrate superior killing of cancer cell lines with low neoantigen density in vitro and improved tumor control in mouse models compared to CAR-T and TRuC-T cells. These findings highlight CAR sensitivity limitations and present STARs as more effective synthetic receptors for T cell-based immunotherapy against tumors with low neoantigen density.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114949"},"PeriodicalIF":7.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615379","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

Rab11-Rab8 cascade dynamics in primary cilia and membrane tubules. 初级纤毛和膜管中的 Rab11-Rab8 级联动力学

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-08 DOI: 10.1016/j.celrep.2024.114955

Ipsita Saha, Christine Insinna, Christopher J Westlake

引用次数: 0

Mapping the gut microbial structural variations in healthy aging within the Chinese population. 绘制中国人群健康老龄化过程中的肠道微生物结构变异图。

IF 7.5 1区生物学

Cell reports Pub Date : 2024-11-08 DOI: 10.1016/j.celrep.2024.114968

Luqi Shen, Hui Zhao, Yue Xi, Zhaoping Wang, Kui Deng, Wanglong Gou, Ke Zhang, Wei Hu, Jun Tang, Fengzhe Xu, Zengliang Jiang, Yuanqing Fu, Yimin Zhu, Dan Zhou, Yu-Ming Chen, Ju-Sheng Zheng

{"title":"Mapping the gut microbial structural variations in healthy aging within the Chinese population.","authors":"Luqi Shen, Hui Zhao, Yue Xi, Zhaoping Wang, Kui Deng, Wanglong Gou, Ke Zhang, Wei Hu, Jun Tang, Fengzhe Xu, Zengliang Jiang, Yuanqing Fu, Yimin Zhu, Dan Zhou, Yu-Ming Chen, Ju-Sheng Zheng","doi":"10.1016/j.celrep.2024.114968","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114968","url":null,"abstract":"Mapping gut microbial structural variants (SVs) during human aging may provide fundamental knowledge and mechanistic understanding of the gut microbiome's relationship with healthy aging. We characterize gut microbial SVs from 3,230 Chinese participants, identifying key SVs associated with aging, healthy aging, and age-related chronic diseases. Our findings reveal a pattern of copy number loss in aging-related SVs, with 35 core SVs consistently detected. Additionally, eight SVs distinguish healthy from unhealthy aging, regardless of age. Notably, a 3-kbp deletion SV of Bifidobacterium pseudocatenulatum, encoding plant polysaccharide degradation, is regulated by plant-based diet and contributes to healthy aging through bile acid metabolism. Our analysis also connects SVs to age-related diseases, such as chronic kidney disease, via genes in the methionine-homocysteine pathway. This study deepens our understanding of the gut microbiome's role in aging and could inform future efforts to enhance lifespan and healthspan.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114968"},"PeriodicalIF":7.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614417","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