Cell Research最新文献_第10页

Modern biology of extrachromosomal DNA: A decade-long voyage of discovery 染色体外DNA的现代生物学：长达十年的发现之旅

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-03 DOI: 10.1038/s41422-024-01054-8

Qing-Lin Yang, Yipeng Xie, Kailiang Qiao, Jun Yi Stanley Lim, Sihan Wu

{"title":"Modern biology of extrachromosomal DNA: A decade-long voyage of discovery","authors":"Qing-Lin Yang, Yipeng Xie, Kailiang Qiao, Jun Yi Stanley Lim, 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}

引用次数: 0

Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism 神经紧张素-脂肪细胞中的神经紧张素受体2信号通过调节神经酰胺代谢来抑制食物摄入

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-03 DOI: 10.1038/s41422-024-01038-8

Wei Fu, Yuanting Lai, Kexin Li, Yue Yang, Xiao Guo, Qifan Gong, Xiaofeng Zhou, Liying Zhou, Cenxi Liu, Zhi Zhang, Jisun So, Yufeng Zhang, Lin Huang, Guangxing Lu, Chuanyou Yi, Qichu Wang, Chenyu Fan, Chao Liu, Jiaxing Wang, Haiyi Yu, Yimin Zhao, Tao Huang, Hyun Cheol Roh, Tiemin Liu, Huiru Tang, Jianping Qi, Ming Xu, Yan Zheng, He Huang, Jin Li

{"title":"Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism","authors":"Wei Fu, Yuanting Lai, Kexin Li, Yue Yang, Xiao Guo, Qifan Gong, Xiaofeng Zhou, Liying Zhou, Cenxi Liu, Zhi Zhang, Jisun So, Yufeng Zhang, Lin Huang, Guangxing Lu, Chuanyou Yi, Qichu Wang, Chenyu Fan, Chao Liu, Jiaxing Wang, Haiyi Yu, Yimin Zhao, Tao Huang, Hyun Cheol Roh, Tiemin Liu, Huiru Tang, Jianping Qi, Ming Xu, Yan Zheng, He Huang, 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 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}

引用次数: 0

Neurotensin signaling in fat modulates food intake 脂肪中的神经紧张素信号调节食物摄入

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-03 DOI: 10.1038/s41422-024-01048-6

YoungUk Jang, Prashant Rajbhandari

引用次数: 0

Donor MHC-specific thymus vaccination allows for immunocompatible allotransplantation 供体mhc特异性胸腺疫苗允许免疫兼容异体移植

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-03 DOI: 10.1038/s41422-024-01049-5

Yang Liu, Hexi Feng, Ke Li, Ruiyi Li, Xiao-Jie Zhang, Ye Tian, Yujiang Fang, Yanjie Zhou, Ling Liu, Xiaoqing Zhang

{"title":"Donor MHC-specific thymus vaccination allows for immunocompatible allotransplantation","authors":"Yang Liu, Hexi Feng, Ke Li, Ruiyi Li, Xiao-Jie Zhang, Ye Tian, Yujiang Fang, Yanjie Zhou, Ling Liu, 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 DMTV 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}

引用次数: 0

LKB1 inactivation unleashes prostate cancer lineage plasticity LKB1失活释放前列腺癌谱系可塑性

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-02 DOI: 10.1038/s41422-024-01030-2

Shaghayegh Nouruzi, Amina Zoubeidi

引用次数: 0

LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer LKB1失活促进前列腺癌表观遗传重塑诱导的谱系可塑性和抗雄激素抗性

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-02 DOI: 10.1038/s41422-024-01025-z

Fei Li, Pengfei Dai, Huili Shi, Yajuan Zhang, Juan He, Anuradha Gopalan, Dan Li, Yu Chen, Yarui Du, Guoliang Xu, Weiwei Yang, Chao Liang, Dong Gao

{"title":"LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer","authors":"Fei Li, Pengfei Dai, Huili Shi, Yajuan Zhang, Juan He, Anuradha Gopalan, Dan Li, Yu Chen, Yarui Du, Guoliang Xu, Weiwei Yang, Chao Liang, 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}

引用次数: 0

Tau(t)ing glucocorticoid binding Tau(t)与糖皮质激素结合

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-02 DOI: 10.1038/s41422-024-01041-z

Sabine Vettorazzi, Jan Tuckermann

引用次数: 0

Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice 减少功能缺陷的老年造血干细胞可减轻老年受体小鼠的衰老相关表型

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-02 DOI: 10.1038/s41422-024-01057-5

Yuting Wang, Wenhao Zhang, Chao Zhang, Hoang Q. Tran Van, Takashi Seino, Yi Zhang

{"title":"Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice","authors":"Yuting Wang, Wenhao Zhang, Chao Zhang, Hoang Q. Tran Van, Takashi Seino, Yi Zhang","doi":"10.1038/s41422-024-01057-5","DOIUrl":"10.1038/s41422-024-01057-5","url":null,"abstract":"Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Developing effective anti-aging strategies is of great significance. In this study, we demonstrated that transplantation of young hematopoietic stem cells (HSCs) into old mice can mitigate aging phenotypes, underscoring the crucial role of HSCs in the aging process. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit “younger” molecular profiles and functions, marked by low levels of CD150 expression. Mechanistically, CD150low HSCs from old mice but not their CD150high counterparts can effectively differentiate into downstream lineage cells. Notably, transplantation of old CD150low HSCs attenuates aging phenotypes and prolongs lifespan of elderly mice compared to those transplanted with unselected or CD150high HSCs. Importantly, reducing the dysfunctional CD150high HSCs can alleviate aging phenotypes in old recipient mice. Thus, our study demonstrates the presence of “younger” HSCs in old mice, and that aging-associated functional decline can be mitigated by reducing dysfunctional HSCs.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 1","pages":"45-58"},"PeriodicalIF":28.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01057-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911415","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}

引用次数: 0

Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss Tau蛋白是一种对糖皮质激素亲和力较低的受体，是糖皮质激素诱导的骨质流失所必需的

IF 28.1 1区生物学

Cell Research Pub Date : 2025-01-02 DOI: 10.1038/s41422-024-01016-0

Wenyu Fu, Meng Chen, Kaidi Wang, Yujianan Chen, Yazhou Cui, Yangli Xie, Zi-Ning Lei, Wenhuo Hu, Guodong Sun, Guiwu Huang, Chaopeng He, Jackie Fretz, Aubryanna Hettinghouse, Ronghan Liu, Xianyi Cai, Mingshuang Zhang, Yuehong Chen, Nan Jiang, Minchun He, Daniel H. Wiznia, Huiyun Xu, Zhe-Sheng Chen, Lin Chen, Kanglai Tang, Hong Zhou, Chuan-Ju Liu

{"title":"Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss","authors":"Wenyu Fu, Meng Chen, Kaidi Wang, Yujianan Chen, Yazhou Cui, Yangli Xie, Zi-Ning Lei, Wenhuo Hu, Guodong Sun, Guiwu Huang, Chaopeng He, Jackie Fretz, Aubryanna Hettinghouse, Ronghan Liu, Xianyi Cai, Mingshuang Zhang, Yuehong Chen, Nan Jiang, Minchun He, Daniel H. Wiznia, Huiyun Xu, Zhe-Sheng Chen, Lin Chen, Kanglai Tang, Hong Zhou, Chuan-Ju Liu","doi":"10.1038/s41422-024-01016-0","DOIUrl":"10.1038/s41422-024-01016-0","url":null,"abstract":"Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with the underlying mechanisms still not fully understood. In this study, we identify Tau as a low-affinity binding receptor for GCs that plays a crucial role in GIO. Tau deficiency largely abolished bone loss induced by high-dose dexamethasone, a synthetic GC, in both inflammatory arthritis and GIO models. Furthermore, TRx0237, a Tau inhibitor identified from an FDA-approved drug library, effectively prevented GIO. Notably, combinatorial administration of TRx0237 and dexamethasone completely overcame the osteoporosis adverse effect of dexamethasone in treating inflammatory arthritis. These findings present Tau as a previously unrecognized GC receptor with low affinity, and provide potential strategies to mitigate a spectrum of GC-related adverse effects, particularly osteoporosis.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"35 1","pages":"23-44"},"PeriodicalIF":28.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-01016-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911556","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}

引用次数: 0

Heat acclimation in mice requires preoptic BDNF neurons and postsynaptic potentiation 小鼠热适应需要视前BDNF神经元和突触后增强

IF 28.1 1区生物学

Cell Research Pub Date : 2024-12-26 DOI: 10.1038/s41422-024-01064-6

Baoting Chen, Cuicui Gao, Changhao Liu, Tongtong Guo, Junwei Hu, Jialiang Xue, Kangmin Tang, Yuelai Chen, Tian Yu, Qiwei Shen, Hongbin Sun, Wen Z. Yang, Wei L. Shen

引用次数: 0