Cell systems最新文献_第6页

Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening. 全基因组光池筛选鉴定细胞内STING转运调节因子的分类和功能表征。

Cell systems Pub Date : 2024-12-18 Epub Date: 2024-12-09 DOI: 10.1016/j.cels.2024.11.004

Matteo Gentili, Rebecca J Carlson, Bingxu Liu, Quentin Hellier, Jocelyn Andrews, Yue Qin, Paul C Blainey, Nir Hacohen

{"title":"Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.","authors":"Matteo Gentili, Rebecca J Carlson, Bingxu Liu, Quentin Hellier, Jocelyn Andrews, Yue Qin, Paul C Blainey, Nir Hacohen","doi":"10.1016/j.cels.2024.11.004","DOIUrl":"10.1016/j.cels.2024.11.004","url":null,"abstract":"Stimulator of interferon genes (STING) traffics across intracellular compartments to trigger innate responses. Mutations in factors regulating this process lead to inflammatory disorders. To systematically identify factors involved in STING trafficking, we performed a genome-wide optical pooled screen (OPS). Based on the subcellular localization of STING in 45 million cells, we defined 464 clusters of gene perturbations based on their cellular phenotypes. A secondary, higher-dimensional OPS identified 73 finer clusters. We show that the loss of the gene of unknown function C19orf25, which clustered with USE1, a protein involved in Golgi-to-endoplasmic reticulum (ER) transport, enhances STING signaling. Additionally, HOPS deficiency delayed STING degradation and consequently increased signaling. Similarly, GARP/RIC1-RGP1 loss increased STING signaling by delaying STING Golgi exit. Our findings demonstrate that genome-wide genotype-phenotype maps based on high-content cell imaging outperform other screening approaches and provide a community resource for mining factors that impact STING trafficking and other cellular processes.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1264-1277.e8"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic immunoengineering approaches to enhance CD8⁺ T cell-based cancer immunotherapy. 代谢免疫工程方法增强基于CD8+ T细胞的癌症免疫治疗。

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.010

Bing Feng, Rongrong Li, Weilin Li, Li Tang

引用次数: 0

Predicting adaptive immune receptor specificities by machine learning is a data generation problem. 通过机器学习预测适应性免疫受体特异性是一个数据生成问题。

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.008

Derek M Mason, Sai T Reddy

引用次数: 0

Turing patterns with cellular computers. 图灵模式与细胞计算机。

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.015

Lewis Grozinger, Ángel Goñi-Moreno

引用次数: 0

Tumor architecture and emergence of strong genetic alterations are bottlenecks for clonal evolution in primary prostate cancer. 肿瘤结构和强基因改变的出现是原发性前列腺癌克隆进化的瓶颈。

Cell systems Pub Date : 2024-11-20 Epub Date: 2024-11-13 DOI: 10.1016/j.cels.2024.10.005

Florian Kreten, Reinhard Büttner, Martin Peifer, Christian Harder, Axel M Hillmer, Nima Abedpour, Anton Bovier, Yuri Tolkach

{"title":"Tumor architecture and emergence of strong genetic alterations are bottlenecks for clonal evolution in primary prostate cancer.","authors":"Florian Kreten, Reinhard Büttner, Martin Peifer, Christian Harder, Axel M Hillmer, Nima Abedpour, Anton Bovier, Yuri Tolkach","doi":"10.1016/j.cels.2024.10.005","DOIUrl":"10.1016/j.cels.2024.10.005","url":null,"abstract":"Prostate cancer (PCA) exhibits high levels of intratumoral heterogeneity. In this study, we developed a mathematical model to study the growth and genetic evolution of PCA. We explored the possible evolutionary patterns and demonstrated that tumor architecture represents a major bottleneck for divergent clonal evolution. Early consecutive acquisition of strong genetic alterations serves as a proxy for the formation of aggressive tumors. A limited number of clonal hierarchy patterns were identified. A biopsy study of synthetic tumors shows complex spatial intermixing of clones and delineates the importance of biopsy extent. Deep whole-exome multiregional next-generation DNA sequencing of the primary tumors from five patients was performed to validate the results, supporting our main findings from mathematical modeling. In conclusion, our model provides qualitatively realistic predictions of PCA genomic evolution, closely aligned with the evidence available from patient samples. We share the code of the model for further studies. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1061-1074.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systematic analysis identifies a connection between spatial and genomic variations of chromatin states. 系统分析确定了染色质状态的空间变化与基因组变化之间的联系。

Cell systems Pub Date : 2024-11-20 Epub Date: 2024-11-13 DOI: 10.1016/j.cels.2024.10.006

Xuan Cao, Terry Ma, Rong Fan, Guo-Cheng Yuan

{"title":"Systematic analysis identifies a connection between spatial and genomic variations of chromatin states.","authors":"Xuan Cao, Terry Ma, Rong Fan, Guo-Cheng Yuan","doi":"10.1016/j.cels.2024.10.006","DOIUrl":"10.1016/j.cels.2024.10.006","url":null,"abstract":"Chromatin states play important roles in the maintenance of cell identities, yet their spatial patterns remain poorly characterized at the organism scale. We developed a systematic approach to analyzing spatial epigenomic data and then applied it to a recently published spatial-CUT&Tag dataset that was obtained from a mouse embryo. We identified a set of spatial genes whose H3K4me3 patterns delineate tissue boundaries. These genes are enriched with tissue-specific transcription factors, and their corresponding genomic loci are marked by broad H3K4me3 domains. Integrative analysis with H3K27me3 profiles showed coordinated spatial transitions across tissue boundaries, which is marked by the continuous shortening of H3K4me3 domains and expansion of H3K27me3 domains. Motif-based analysis identified transcription factors whose activities change significantly during such transitions. Taken together, our systematic analyses reveal a strong connection between the genomic and spatial variations of chromatin states. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1092-1102.e2"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systematic screens for fertility genes essential for malaria parasite transmission reveal conserved aspects of sex in a divergent eukaryote. 对疟原虫传播所必需的生育基因进行系统筛选，揭示了真核生物在性方面的保守性。

Cell systems Pub Date : 2024-11-20 Epub Date: 2024-11-13 DOI: 10.1016/j.cels.2024.10.008

Claire Sayers, Vikash Pandey, Arjun Balakrishnan, Katharine Michie, Dennis Svedberg, Mirjam Hunziker, Mercedes Pardo, Jyoti Choudhary, Ronnie Berntsson, Oliver Billker

{"title":"Systematic screens for fertility genes essential for malaria parasite transmission reveal conserved aspects of sex in a divergent eukaryote.","authors":"Claire Sayers, Vikash Pandey, Arjun Balakrishnan, Katharine Michie, Dennis Svedberg, Mirjam Hunziker, Mercedes Pardo, Jyoti Choudhary, Ronnie Berntsson, Oliver Billker","doi":"10.1016/j.cels.2024.10.008","DOIUrl":"10.1016/j.cels.2024.10.008","url":null,"abstract":"Sexual reproduction in malaria parasites is essential for their transmission to mosquitoes and offers a divergent eukaryote model to understand the evolution of sex. Through a panel of genetic screens in Plasmodium berghei, we identify 348 sex and transmission-related genes and define roles for unstudied genes as putative targets for transmission-blocking interventions. The functional data provide a deeper understanding of female metabolic reprogramming, meiosis, and the axoneme. We identify a complex of a SUN domain protein (SUN1) and a putative allantoicase (ALLC1) that is essential for male fertility by linking the microtubule organizing center to the nuclear envelope and enabling mitotic spindle formation during male gametogenesis. Both proteins have orthologs in mouse testis, and the data raise the possibility of an ancient role for atypical SUN domain proteins in coupling the nucleus and axoneme. Altogether, our data provide an unbiased picture of the molecular processes that underpin malaria parasite transmission. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1075-1091.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The master regulator OxyR orchestrates bacterial oxidative stress response genes in space and time. 主调控因子 OxyR 在空间和时间上协调细菌氧化应激反应基因。

Cell systems Pub Date : 2024-11-20 DOI: 10.1016/j.cels.2024.10.003

Divya Choudhary, Kevin R Foster, Stephan Uphoff

{"title":"The master regulator OxyR orchestrates bacterial oxidative stress response genes in space and time.","authors":"Divya Choudhary, Kevin R Foster, Stephan Uphoff","doi":"10.1016/j.cels.2024.10.003","DOIUrl":"10.1016/j.cels.2024.10.003","url":null,"abstract":"Bacteria employ diverse gene regulatory networks to survive stress, but deciphering the underlying logic of these complex networks has proved challenging. Here, we use time-resolved single-cell imaging to explore the functioning of the E. coli regulatory response to oxidative stress. We observe diverse gene expression dynamics within the network. However, by controlling for stress-induced growth-rate changes, we show that these patterns involve just three classes of regulation: downregulated genes, upregulated pulsatile genes, and gradually upregulated genes. The two upregulated classes are distinguished by differences in the binding of the transcription factor, OxyR, and appear to play distinct roles during stress protection. Pulsatile genes activate transiently in a few cells for initial protection of a group of cells, whereas gradually upregulated genes induce evenly, generating a lasting protection involving many cells. Our study shows how bacterial populations use simple regulatory principles to coordinate stress responses in space and time. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1033-1045.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AlphaFold opens the doors to deorphanizing secreted proteins. AlphaFold 打开了分泌蛋白去形态化的大门。

Cell systems Pub Date : 2024-11-20 DOI: 10.1016/j.cels.2024.10.010

Shruthi Viswanath

引用次数: 0

How can concepts from ecology enable insights about cellular communities? 生态学的概念如何帮助我们了解细胞群落？

Cell systems Pub Date : 2024-11-20 Epub Date: 2024-11-07 DOI: 10.1016/j.cels.2024.10.009

Anna Weiss, Matti Gralka, Karoline Faust, David Basanta Gutierrez, Kenneth Pienta, Xu Zhou, Ophelia S Venturelli, Sean Gibbons, Mo Ebrahimkhani, Nika Shakiba, Shaohua Ma

引用次数: 0