Cell systems最新文献_第2页

Emerging approaches for T cell-stimulating platform development.

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.007

Emily Ariail, Nikol Garcia Espinoza, A Carson Stephenson, Jamie B Spangler

引用次数: 0

What unique insights can modeling approaches capture about the immune system?

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.016

Hao Yuan Kueh, Andreas Handel, Alexander Hoffmann, Diego Chowell, Rachel A Gottschalk, Harinder Singh, Ronald N Germain, Martin Meier-Schellersheim, Kathryn Miller-Jensen, Grégoire Altan-Bonnet

引用次数: 0

Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.

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.

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.

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.

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

Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome.

Cell systems Pub Date : 2024-12-14 DOI: 10.1016/j.cels.2024.12.002

Eli Metzner, Kaden M Southard, Thomas M Norman

{"title":"Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome.","authors":"Eli Metzner, Kaden M Southard, Thomas M Norman","doi":"10.1016/j.cels.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.cels.2024.12.002","url":null,"abstract":"Single-cell CRISPR screens link genetic perturbations to transcriptional states, but high-throughput methods connecting these induced changes to their regulatory foundations are limited. Here, we introduce Multiome Perturb-seq, extending single-cell CRISPR screens to simultaneously measure perturbation-induced changes in gene expression and chromatin accessibility. We apply Multiome Perturb-seq in a CRISPRi screen of 13 chromatin remodelers in human RPE-1 cells, achieving efficient assignment of sgRNA identities to single nuclei via an improved method for capturing barcode transcripts from nuclear RNA. We organize expression and accessibility measurements into coherent programs describing the integrated effects of perturbations on cell state, finding that ARID1A and SUZ12 knockdowns induce programs enriched for developmental features. Modeling of perturbation-induced heterogeneity connects accessibility changes to changes in gene expression, highlighting the value of multimodal profiling. Overall, our method provides a scalable and simply implemented system to dissect the regulatory logic underpinning cell state. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848688","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

Stochastic modeling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.

Cell systems Pub Date : 2024-12-12 DOI: 10.1016/j.cels.2024.11.013

M G Hirsch, Soumitra Pal, Farid Rashidi Mehrabadi, Salem Malikic, Charli Gruen, Antonella Sassano, Eva Pérez-Guijarro, Glenn Merlino, S Cenk Sahinalp, Erin K Molloy, Chi-Ping Day, Teresa M Przytycka

{"title":"Stochastic modeling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.","authors":"M G Hirsch, Soumitra Pal, Farid Rashidi Mehrabadi, Salem Malikic, Charli Gruen, Antonella Sassano, Eva Pérez-Guijarro, Glenn Merlino, S Cenk Sahinalp, Erin K Molloy, Chi-Ping Day, Teresa M Przytycka","doi":"10.1016/j.cels.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.cels.2024.11.013","url":null,"abstract":"Cancer progression is an evolutionary process driven by the selection of cells adapted to gain growth advantage. We present a formal study on the adaptation of gene expression in subclonal evolution. We model evolutionary changes in gene expression as stochastic Ornstein-Uhlenbeck processes, jointly leveraging the evolutionary history of subclones and single-cell expression data. Applying our model to sublines derived from single cells of a mouse melanoma revealed that sublines with distinct phenotypes are underlined by different patterns of gene expression adaptation, indicating non-genetic mechanisms of cancer evolution. Sublines previously observed to be resistant to anti-CTLA4 treatment showed adaptive expression of genes related to invasion and non-canonical Wnt signaling, whereas sublines that responded to treatment showed adaptive expression of genes related to proliferation and canonical Wnt signaling. Our results suggest that clonal phenotypes emerge as the result of specific adaptivity patterns of gene expression. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866641","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

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