Cell Research最新文献_第10页

Aberrant phase separation: linking IDR mutations to disease 异常相分离：将IDR突变与疾病联系起来。

IF 44.1 1区生物学

Cell Research Pub Date : 2023-04-04 DOI: 10.1038/s41422-023-00804-4

Rashik Ahmed, Julie D. Forman-Kay

引用次数: 0

Positively charged patches: tonic for CAR fitness 正电荷贴片：CAR健身的补品。

IF 44.1 1区生物学

Cell Research Pub Date : 2023-04-04 DOI: 10.1038/s41422-023-00803-5

Meraj H. Khan, Jan Joseph Melenhorst

引用次数: 0

Activation of lineage competence in hemogenic endothelium precedes the formation of hematopoietic stem cell heterogeneity 在造血干细胞异质性形成之前激活造血内皮的系系能力

IF 44.1 1区生物学

Cell Research Pub Date : 2023-04-04 DOI: 10.1038/s41422-023-00797-0

Jun Xia, Mengyao Liu, Caiying Zhu, Shicheng Liu, Lanlan Ai, Dongyuan Ma, Ping Zhu, Lu Wang, Feng Liu

{"title":"Activation of lineage competence in hemogenic endothelium precedes the formation of hematopoietic stem cell heterogeneity","authors":"Jun Xia, Mengyao Liu, Caiying Zhu, Shicheng Liu, Lanlan Ai, Dongyuan Ma, Ping Zhu, Lu Wang, Feng Liu","doi":"10.1038/s41422-023-00797-0","DOIUrl":"10.1038/s41422-023-00797-0","url":null,"abstract":"Hematopoietic stem and progenitor cells (HSPCs) are considered as a heterogeneous population, but precisely when, where and how HSPC heterogeneity arises remain largely unclear. Here, using a combination of single-cell multi-omics, lineage tracing and functional assays, we show that embryonic HSPCs originate from heterogeneous hemogenic endothelial cells (HECs) during zebrafish embryogenesis. Integrated single-cell transcriptome and chromatin accessibility analysis demonstrates transcriptional heterogeneity and regulatory programs that prime lymphoid/myeloid fates at the HEC level. Importantly, spi2+ HECs give rise to lymphoid/myeloid-primed HSPCs (L/M-HSPCs) and display a stress-responsive function under acute inflammation. Moreover, we uncover that Spi2 is required for the formation of L/M-HSPCs through tightly controlling the endothelial-to-hematopoietic transition program. Finally, single-cell transcriptional comparison of zebrafish and human HECs and human induced pluripotent stem cell-based hematopoietic differentiation results support the evolutionary conservation of L/M-HECs and a conserved role of SPI1 (spi2 homolog in mammals) in humans. These results unveil the lineage origin, biological function and molecular determinant of HSPC heterogeneity and lay the foundation for new strategies for induction of transplantable lineage-primed HSPCs in vitro.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"33 6","pages":"448-463"},"PeriodicalIF":44.1,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9705118","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: 5

Transgenerational inheritance of engineered cytosine methylation in mice 小鼠工程胞嘧啶甲基化的跨代遗传。

IF 44.1 1区生物学

Cell Research Pub Date : 2023-04-03 DOI: 10.1038/s41422-023-00799-y

Maximilian M. L. Knott, Oded Rechavi

引用次数: 0

Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial 基于亚型分析的平台为重度预处理转移性三阴性乳腺癌的精准医疗提供指导：FUTURE II 期总体临床试验

IF 44.1 1区生物学

Cell Research Pub Date : 2023-03-27 DOI: 10.1038/s41422-023-00795-2

Yin Liu, Xiu-Zhi Zhu, Yi Xiao, Song-Yang Wu, Wen-Jia Zuo, Qiang Yu, A-Yong Cao, Jun-Jie Li, Ke-Da Yu, Guang-Yu Liu, Jiong Wu, Tao Sun, Jiu-Wei Cui, Zheng Lv, Hui-Ping Li, Xiao-Yu Zhu, Yi-Zhou Jiang, Zhong-Hua Wang, Zhi-Ming Shao

{"title":"Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial","authors":"Yin Liu, Xiu-Zhi Zhu, Yi Xiao, Song-Yang Wu, Wen-Jia Zuo, Qiang Yu, A-Yong Cao, Jun-Jie Li, Ke-Da Yu, Guang-Yu Liu, Jiong Wu, Tao Sun, Jiu-Wei Cui, Zheng Lv, Hui-Ping Li, Xiao-Yu Zhu, Yi-Zhou Jiang, Zhong-Hua Wang, Zhi-Ming Shao","doi":"10.1038/s41422-023-00795-2","DOIUrl":"10.1038/s41422-023-00795-2","url":null,"abstract":"Triple-negative breast cancer (TNBC) is a heterogeneous disease and lacks effective treatment. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we report the final results of FUTURE, a phase II umbrella trial designed to explore whether the subtyping-based strategy may improve the outcomes in metastatic TNBC patients. A total of 141 patients with a median of three previous lines of therapies in the metastatic setting were enrolled in seven parallel arms. Confirmed objective responses were achieved in 42 patients (29.8%; 95% confidence interval [CI], 22.4–38.1). The median values of progression-free survival and overall survival were 3.4 (95% CI: 2.7–4.2) and 10.7 (95% CI: 9.1–12.3) months, respectively. Given Bayesian predictive probability, efficacy boundaries were achieved in four arms. Furthermore, integrated genomic and clinicopathological profiling illustrated associations of clinical and genomic parameters with treatment efficacy, and the efficacy of novel antibody–drug conjugates was explored in preclinical TNBC models of subtypes for which treatment was futile. In general, the FUTURE strategy recruits patients efficiently and provides promising efficacy with manageable toxicities, outlining a direction for further clinical exploration.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"33 5","pages":"389-402"},"PeriodicalIF":44.1,"publicationDate":"2023-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10156707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9766763","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: 2

Cryo-EM structures of human monkeypox viral replication complexes with and without DNA duplex 有 DNA 双链和无 DNA 双链的人猴痘病毒复制复合物的冷冻电镜结构。

IF 44.1 1区生物学

Cell Research Pub Date : 2023-03-27 DOI: 10.1038/s41422-023-00796-1

Yunxia Xu, Yaqi Wu, Yuanyuan Zhang, Ruixin Fan, Yaxue Yang, Danyang Li, Shimin Zhu, Biao Yang, Zhengyu Zhang, Changjiang Dong

引用次数: 3

H3K4me2/3 modulate the stability of RNA polymerase II pausing H3K4me2/3调节RNA聚合酶II暂停的稳定性。

IF 44.1 1区生物学

Cell Research Pub Date : 2023-03-15 DOI: 10.1038/s41422-023-00794-3

Shibin Hu, Aixia Song, Linna Peng, Nan Tang, Zhibin Qiao, Zhenning Wang, Fei Lan, Fei Xavier Chen

引用次数: 2

Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness 调节嵌合抗原受体的电荷密度可优化营养信号传递和 CAR-T 细胞的适应性

IF 44.1 1区生物学

Cell Research Pub Date : 2023-03-08 DOI: 10.1038/s41422-023-00789-0

Jian Chen, Shizhen Qiu, Wentao Li, Kun Wang, Yu Zhang, Han Yang, Baichuan Liu, Guangfei Li, Li Li, Min Chen, Junjie Lan, Jiahua Niu, Peijie He, Lei Cheng, Gaofeng Fan, Xin Liu, Xianmin Song, Chenqi Xu, Haitao Wu, Haopeng Wang

{"title":"Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness","authors":"Jian Chen, Shizhen Qiu, Wentao Li, Kun Wang, Yu Zhang, Han Yang, Baichuan Liu, Guangfei Li, Li Li, Min Chen, Junjie Lan, Jiahua Niu, Peijie He, Lei Cheng, Gaofeng Fan, Xin Liu, Xianmin Song, Chenqi Xu, Haitao Wu, Haopeng Wang","doi":"10.1038/s41422-023-00789-0","DOIUrl":"10.1038/s41422-023-00789-0","url":null,"abstract":"Tonic signaling of chimeric antigen receptor (CAR), i.e., the spontaneous CAR activation in the absence of tumor antigen stimulation, is considered to be a pivotal event controlling CAR-T efficacy. However, the molecular mechanism underlying the spontaneous CAR signals remains elusive. Here, we unveil that positively charged patches (PCPs) on the surface of the CAR antigen-binding domain mediate CAR clustering and result in CAR tonic signaling. For CARs with high tonic signaling (e.g., GD2.CAR and CSPG4.CAR), reducing PCPs on CARs or boosting ionic strength in the culture medium during ex vivo CAR-T cell expansion minimizes spontaneous CAR activation and alleviates CAR-T cell exhaustion. In contrast, introducing PCPs into the CAR with weak tonic signaling, such as CD19.CAR, results in improved in vivo persistence and superior antitumor function. These results demonstrate that CAR tonic signaling is induced and maintained by PCP-mediated CAR clustering. Notably, the mutations we generated to alter the PCPs maintain the antigen-binding affinity and specificity of the CAR. Therefore, our findings suggest that the rational tuning of PCPs to optimize tonic signaling and in vivo fitness of CAR-T cells is a promising design strategy for the next-generation CAR.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"33 5","pages":"341-354"},"PeriodicalIF":44.1,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10156745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9414462","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: 15

Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner NAT10 的赖氨酸 2-羟基异丁酰化以依赖于 ac4C 的方式促进癌症转移

IF 44.1 1区生物学

Cell Research Pub Date : 2023-03-08 DOI: 10.1038/s41422-023-00793-4

Long Liao, Yan He, Shu-Jun Li, Xiao-Mei Yu, Zhi-Chao Liu, Yi-Yao Liang, Han Yang, Jing Yang, Guo-Geng Zhang, Chun-Miao Deng, Xian Wei, Yi-Dong Zhu, Tao-Yang Xu, Can-Can Zheng, Chao Cheng, Ang Li, Zhi-Gang Li, Jin-Bao Liu, Bin Li

{"title":"Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner","authors":"Long Liao, Yan He, Shu-Jun Li, Xiao-Mei Yu, Zhi-Chao Liu, Yi-Yao Liang, Han Yang, Jing Yang, Guo-Geng Zhang, Chun-Miao Deng, Xian Wei, Yi-Dong Zhu, Tao-Yang Xu, Can-Can Zheng, Chao Cheng, Ang Li, Zhi-Gang Li, Jin-Bao Liu, Bin Li","doi":"10.1038/s41422-023-00793-4","DOIUrl":"10.1038/s41422-023-00793-4","url":null,"abstract":"Posttranslational modifications add tremendous complexity to proteomes; however, gaps remain in knowledge regarding the function and regulatory mechanism of newly discovered lysine acylation modifications. Here, we compared a panel of non-histone lysine acylation patterns in metastasis models and clinical samples, and focused on 2-hydroxyisobutyrylation (Khib) due to its significant upregulation in cancer metastases. By the integration of systemic Khib proteome profiling in 20 paired primary esophageal tumor and metastatic tumor tissues with CRISPR/Cas9 functional screening, we identified N-acetyltransferase 10 (NAT10) as a substrate for Khib modification. We further showed that Khib modification at lysine 823 in NAT10 functionally contribute to metastasis. Mechanistically, NAT10 Khib modification enhances its interaction with deubiquitinase USP39, resulting in increased NAT10 protein stability. NAT10 in turn promotes metastasis by increasing NOTCH3 mRNA stability in an N4-acetylcytidine-dependent manner. Furthermore, we discovered a lead compound #7586-3507 that inhibited NAT10 Khib modification and showed efficacy in tumor models in vivo at a low concentration. Together, our findings bridge newly identified lysine acylation modifications with RNA modifications, thus providing novel insights into epigenetic regulation in human cancer. We propose that pharmacological inhibition of NAT10 K823 Khib modification constitutes a potential anti-metastasis strategy.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"33 5","pages":"355-371"},"PeriodicalIF":44.1,"publicationDate":"2023-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9414463","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: 8

Polyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens 多价 mRNA 疫苗接种可激发对猴痘病毒表面抗原的强效免疫反应

IF 44.1 1区生物学

Cell Research Pub Date : 2023-03-06 DOI: 10.1038/s41422-023-00792-5

Zhenhao Fang, Valter S. Monteiro, Paul A. Renauer, Xingbo Shang, Kazushi Suzuki, Xinyu Ling, Meizhu Bai, Yan Xiang, Andre Levchenko, Carmen J. Booth, Carolina Lucas, Sidi Chen

引用次数: 6