Cell Research最新文献

{"title":"The conjugation-associated linear-BAC iterative assembling (CALBIA) method for cloning 2.1-Mb human chromosomal DNAs in bacteria","authors":"Li Zhong, Qi Zhang, Ning Lu, Tao Wang, Xiaoli Xue, Zhongjun Qin","doi":"10.1038/s41422-024-01063-7","DOIUrl":"10.1038/s41422-024-01063-7","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 4","pages":"309-312"},"PeriodicalIF":28.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01063-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929417","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}

{"title":"Nonenzymatic lysine d-lactylation induced by glyoxalase II substrate SLG dampens inflammatory immune responses","authors":"Qihang Zhao, Qiang Wang, Qinghua Yao, Zhengdong Yang, Wenfang Li, Xiaojie Cheng, Yingling Wen, Rong Chen, Junfang Xu, Xuanying Wang, Dexiang Qin, Shuyang Zhu, Liujie He, Nan Li, Yanfeng Wu, Yizhi Yu, Xuetao Cao, Pin Wang","doi":"10.1038/s41422-024-01060-w","DOIUrl":"10.1038/s41422-024-01060-w","url":null,"abstract":"Immunometabolism is critical in the regulation of immunity and inflammation; however, the mechanism of preventing aberrant activation-induced immunopathology remains largely unclear. Here, we report that glyoxalase II (GLO2) in the glycolysis branching pathway is specifically downregulated by NF-κB signaling during innate immune activation via tristetraprolin (TTP)-mediated mRNA decay. As a result, its substrate S-D-lactoylglutathione (SLG) accumulates in the cytosol and directly induces d-lactyllysine modification of proteins. This nonenzymatic lactylation by SLG is greatly facilitated by a nearby cysteine residue, as it initially reacts with SLG to form a reversible S-lactylated thiol intermediate, followed by SN-transfer of the lactyl moiety to a proximal lysine. Lactylome profiling identifies 2255 lactylation sites mostly in cytosolic proteins of activated macrophages, and global protein structure analysis suggests that proximity to a cysteine residue determines the susceptibility of lysine to SLG-mediated d-lactylation. Furthermore, lactylation is preferentially enriched in proteins involved in immune activation and inflammatory pathways, and d-lactylation at lysine 310 (K310) of RelA attenuates inflammatory signaling and NF-κB transcriptional activity to restore immune homeostasis. Accordingly, TTP-binding site mutation or overexpression of GLO2 in vivo blocks this feedback lactylation in innate immune cells and promotes inflammation, whereas genetic deficiency or pharmacological inhibition of GLO2 restricts immune activation and attenuates inflammatory immunopathology both in vitro and in vivo. Importantly, dysregulation of the GLO2/SLG/d-lactylation regulatory axis is closely associated with human inflammatory phenotypes. Overall, our findings uncover an immunometabolic feedback loop of SLG-induced nonenzymatic d-lactylation and implicate GLO2 as a promising target for combating clinical inflammatory disorders.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 2","pages":"97-116"},"PeriodicalIF":28.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01060-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929418","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}

{"title":"Neoself-antigen presentation in SLE: Mordred’s coronation in Arthur’s absence","authors":"Mehrdad Pazhouhandeh, Hongjian Sun, Di Yu","doi":"10.1038/s41422-024-01052-w","DOIUrl":"https://doi.org/10.1038/s41422-024-01052-w","url":null,"abstract":"<p><b>In a recent study led by Dr. Hisashi Arase published in</b> <b><i>Cell</i></b><b>, a new mechanism underlying the breakdown of self-tolerance in systemic lupus erythematosus was reported that autoreactive T cells recognize neoself-antigens. Neoself-antigens, encompassing a range of self-molecules, were shown to be presented on major histocompatibility complex class II by non-canonical mechanisms following the downregulation of the invariant chain protein.</b></p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"48 1","pages":""},"PeriodicalIF":44.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929416","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}

{"title":"Intrathymic alloantigen expression—the Holy Grail or reinventing the wheel?","authors":"Gavin J. Pettigrew","doi":"10.1038/s41422-024-01067-3","DOIUrl":"10.1038/s41422-024-01067-3","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 2","pages":"87-88"},"PeriodicalIF":28.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01067-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929387","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}

{"title":"Modern biology of extrachromosomal DNA: A decade-long voyage of discovery","authors":"Qing-Lin Yang,&nbsp;Yipeng Xie,&nbsp;Kailiang Qiao,&nbsp;Jun Yi Stanley Lim,&nbsp;Sihan Wu","doi":"10.1038/s41422-024-01054-8","DOIUrl":"10.1038/s41422-024-01054-8","url":null,"abstract":"Genomic instability is a hallmark of cancer and is a major driving force of tumorigenesis. A key manifestation of genomic instability is the formation of extrachromosomal DNAs (ecDNAs) — acentric, circular DNA molecules ranging from 50 kb to 5 Mb in size, distinct from chromosomes. Ontological studies have revealed that ecDNA serves as a carrier of oncogenes, immunoregulatory genes, and enhancers, capable of driving elevated transcription of its cargo genes and cancer heterogeneity, leading to rapid tumor evolution and therapy resistance. Although ecDNA was documented over half a century ago, the past decade has witnessed a surge in breakthrough discoveries about its biological functions. Here, we systematically review the modern biology of ecDNA uncovered over the last ten years, focusing on how discoveries during this pioneering stage have illuminated our understanding of ecDNA-driven transcription, heterogeneity, and cancer progression. Furthermore, we discuss ongoing efforts to target ecDNA as a novel approach to cancer therapy. This burgeoning field is entering a new phase, poised to reshape our knowledge of cancer biology and therapeutic strategies.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 1","pages":"11-22"},"PeriodicalIF":28.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01054-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917042","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}

{"title":"Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism","authors":"Wei Fu,&nbsp;Yuanting Lai,&nbsp;Kexin Li,&nbsp;Yue Yang,&nbsp;Xiao Guo,&nbsp;Qifan Gong,&nbsp;Xiaofeng Zhou,&nbsp;Liying Zhou,&nbsp;Cenxi Liu,&nbsp;Zhi Zhang,&nbsp;Jisun So,&nbsp;Yufeng Zhang,&nbsp;Lin Huang,&nbsp;Guangxing Lu,&nbsp;Chuanyou Yi,&nbsp;Qichu Wang,&nbsp;Chenyu Fan,&nbsp;Chao Liu,&nbsp;Jiaxing Wang,&nbsp;Haiyi Yu,&nbsp;Yimin Zhao,&nbsp;Tao Huang,&nbsp;Hyun Cheol Roh,&nbsp;Tiemin Liu,&nbsp;Huiru Tang,&nbsp;Jianping Qi,&nbsp;Ming Xu,&nbsp;Yan Zheng,&nbsp;He Huang,&nbsp;Jin Li","doi":"10.1038/s41422-024-01038-8","DOIUrl":"10.1038/s41422-024-01038-8","url":null,"abstract":"Neurotensin (NTS) is a secretory peptide produced by lymphatic endothelial cells. Our previous study revealed that NTS suppressed the activity of brown adipose tissue via interactions with NTSR2. In the current study, we found that the depletion of Ntsr2 in white adipocytes upregulated food intake, while the local treatment of NTS suppressed food intake. Our mechanistic study revealed that suppression of NTS-NTSR2 signaling enhanced the phosphorylation of ceramide synthetase 2, increased the abundance of its products ceramides C20–C24, and downregulated the production of GDF15 in white adipose tissues, which was responsible for the elevation of food intake. We discovered a potential causal and positive correlation between serum C20–C24 ceramide&nbsp;levels and human food intake in four populations with different ages and ethnic backgrounds. Together, our study shows that NTS-NTSR2 signaling in white adipocytes can regulate food intake via its direct control of lipid metabolism and production of GDF15. The ceramides C20–C24 are key factors regulating food intake in mammals.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 2","pages":"117-131"},"PeriodicalIF":28.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01038-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917054","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}

{"title":"Neurotensin signaling in fat modulates food intake","authors":"YoungUk Jang,&nbsp;Prashant Rajbhandari","doi":"10.1038/s41422-024-01048-6","DOIUrl":"10.1038/s41422-024-01048-6","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 2","pages":"85-86"},"PeriodicalIF":28.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01048-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917018","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}

{"title":"Donor MHC-specific thymus vaccination allows for immunocompatible allotransplantation","authors":"Yang Liu,&nbsp;Hexi Feng,&nbsp;Ke Li,&nbsp;Ruiyi Li,&nbsp;Xiao-Jie Zhang,&nbsp;Ye Tian,&nbsp;Yujiang Fang,&nbsp;Yanjie Zhou,&nbsp;Ling Liu,&nbsp;Xiaoqing Zhang","doi":"10.1038/s41422-024-01049-5","DOIUrl":"10.1038/s41422-024-01049-5","url":null,"abstract":"Organ transplantation is the last-resort option to treat organ failure. However, less than 10% of patients benefit from this only option due to lack of major histocompatibility complex (MHC)-matched donor organs and 25%–80% of donated organs could not find MHC-matched recipients. T cell allorecognition is the principal mechanism for allogeneic graft rejection. We herein present a “donor MHC-specific thymus vaccination” (DMTV) strategy to induce T cell tolerance to both autologous and allogeneic donor MHC. Allogeneic MHC molecules were expressed in the recipient thymus through adeno-associated virus-mediated delivery, which led to stable expression of allogeneic MHC together with the autologous MHC in the engineered thymus. During local T cell education, those T cells recognizing either autologous MHC or allogeneic MHC were equally depleted. We constructed C57BL/6-MHC and BALB/c-MHC dual immunocompatible mice via thymus vaccination of C57BL/6-MHC into the BALB/c thymus and observed long-term graft tolerance after transplantation of C57BL/6 skin and C57BL/6 mouse embryonic stem cells into the vaccinated BALB/c mice. We also validated our DMTV strategy in a bone marrow, liver, thymus (BLT)-humanized mouse model for immunocompatible allotransplantation of human embryonic stem cells. Our study suggests that the&nbsp;DMTV&nbsp;strategy is a potent avenue to introduce a donor compatible immune system in recipients, which overcomes the clinical dilemma of the extreme shortage of MHC-matched donor organs for treating patients with end-stage organ failure.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 2","pages":"132-144"},"PeriodicalIF":28.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01049-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917019","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}

{"title":"LKB1 inactivation unleashes prostate cancer lineage plasticity","authors":"Shaghayegh Nouruzi,&nbsp;Amina Zoubeidi","doi":"10.1038/s41422-024-01030-2","DOIUrl":"10.1038/s41422-024-01030-2","url":null,"abstract":"","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 1","pages":"5-6"},"PeriodicalIF":28.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01030-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911554","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}

{"title":"LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer","authors":"Fei Li,&nbsp;Pengfei Dai,&nbsp;Huili Shi,&nbsp;Yajuan Zhang,&nbsp;Juan He,&nbsp;Anuradha Gopalan,&nbsp;Dan Li,&nbsp;Yu Chen,&nbsp;Yarui Du,&nbsp;Guoliang Xu,&nbsp;Weiwei Yang,&nbsp;Chao Liang,&nbsp;Dong Gao","doi":"10.1038/s41422-024-01025-z","DOIUrl":"10.1038/s41422-024-01025-z","url":null,"abstract":"Epigenetic regulation profoundly influences the fate of cancer cells and their capacity to switch between lineages by modulating essential gene expression, thereby shaping tumor heterogeneity and therapy response. In castration-resistant prostate cancer (CRPC), the intricacies behind androgen receptor (AR)-independent lineage plasticity remain unclear, leading to a scarcity of effective clinical treatments. Utilizing single-cell RNA sequencing on both human and mouse prostate cancer samples, combined with whole-genome bisulfite sequencing and multiple genetically engineered mouse models, we investigated the molecular mechanism of AR-independent lineage plasticity and uncovered a potential therapeutic strategy. Single-cell transcriptomic profiling of human prostate cancers, both pre- and post-androgen deprivation therapy, revealed an association between liver kinase B1 (LKB1) pathway inactivation and AR independence. LKB1 inactivation led to AR-independent lineage plasticity and global DNA hypomethylation during prostate cancer progression. Importantly, the pharmacological inhibition of TET enzymes and supplementation with S-adenosyl methionine were found to effectively suppress AR-independent prostate cancer growth. These insights shed light on the mechanism driving AR-independent lineage plasticity and propose a potential therapeutic strategy by targeting DNA hypomethylation in AR-independent CRPC.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 1","pages":"59-71"},"PeriodicalIF":28.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01025-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911555","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}