Cell systems最新文献_第7页

Simple visualization of submicroscopic protein clusters with a phase-separation-based fluorescent reporter. 利用基于相分离的荧光报告器实现亚显微蛋白质团簇的简单可视化。

Cell systems Pub Date : 2024-06-19 Epub Date: 2024-05-25 DOI: 10.1016/j.cels.2024.05.003

Thomas R Mumford, Diarmid Rae, Emily Brackhahn, Abbas Idris, David Gonzalez-Martinez, Ayush Aditya Pal, Michael C Chung, Juan Guan, Elizabeth Rhoades, Lukasz J Bugaj

引用次数: 0

Tissue module discovery in single-cell-resolution spatial transcriptomics data via cell-cell interaction-aware cell embedding. 通过细胞-细胞交互感知细胞嵌入在单细胞分辨率空间转录组学数据中发现组织模块

Cell systems Pub Date : 2024-06-19 Epub Date: 2024-05-31 DOI: 10.1016/j.cels.2024.05.001

Yuzhe Li, Jinsong Zhang, Xin Gao, Qiangfeng Cliff Zhang

{"title":"Tissue module discovery in single-cell-resolution spatial transcriptomics data via cell-cell interaction-aware cell embedding.","authors":"Yuzhe Li, Jinsong Zhang, Xin Gao, Qiangfeng Cliff Zhang","doi":"10.1016/j.cels.2024.05.001","DOIUrl":"10.1016/j.cels.2024.05.001","url":null,"abstract":"Computational methods are desired for single-cell-resolution spatial transcriptomics (ST) data analysis to uncover spatial organization principles for how individual cells exert tissue-specific functions. Here, we present ST data analysis via interaction-aware cell embedding (SPACE), a deep-learning method for cell-type identification and tissue module discovery from single-cell-resolution ST data by learning a cell representation that captures its gene expression profile and interactions with its spatial neighbors. SPACE identified spatially informed cell subtypes defined by their special spatial distribution patterns and distinct proximal-interacting cell types. SPACE also automatically discovered \"cell communities\"-tissue modules with discernible boundaries and a uniform spatial distribution of constituent cell types. For each cell community, SPACE outputs a characteristic proximal cell-cell interaction network associated with physiological processes, which can be used to refine ligand-receptor-based intercellular signaling analyses. We envision that SPACE can be used in large-scale ST projects to understand how proximal cell-cell interactions contribute to emergent biological functions within cell communities. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"578-592.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186041","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

Stimulus-response signaling dynamics characterize macrophage polarization states. 刺激-反应信号动态描述了巨噬细胞的极化状态。

Cell systems Pub Date : 2024-06-19 Epub Date: 2024-06-05 DOI: 10.1016/j.cels.2024.05.002

Apeksha Singh, Supriya Sen, Michael Iter, Adewunmi Adelaja, Stefanie Luecke, Xiaolu Guo, Alexander Hoffmann

{"title":"Stimulus-response signaling dynamics characterize macrophage polarization states.","authors":"Apeksha Singh, Supriya Sen, Michael Iter, Adewunmi Adelaja, Stefanie Luecke, Xiaolu Guo, Alexander Hoffmann","doi":"10.1016/j.cels.2024.05.002","DOIUrl":"10.1016/j.cels.2024.05.002","url":null,"abstract":"The functional state of cells is dependent on their microenvironmental context. Prior studies described how polarizing cytokines alter macrophage transcriptomes and epigenomes. Here, we characterized the functional responses of 6 differentially polarized macrophage populations by measuring the dynamics of transcription factor nuclear factor κB (NF-κB) in response to 8 stimuli. The resulting dataset of single-cell NF-κB trajectories was analyzed by three approaches: (1) machine learning on time-series data revealed losses of stimulus distinguishability with polarization, reflecting canalized effector functions. (2) Informative trajectory features driving stimulus distinguishability (\"signaling codons\") were identified and used for mapping a cell state landscape that could then locate macrophages conditioned by an unrelated condition. (3) Kinetic parameters, inferred using a mechanistic NF-κB network model, provided an alternative mapping of cell states and correctly predicted biochemical findings. Together, this work demonstrates that a single analyte's dynamic trajectories may distinguish the functional states of single cells and molecular network states underlying them. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"563-577.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11226196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285663","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

The substrate quality of CK2 target sites has a determinant role on their function and evolution. CK2 目标位点的底物质量对其功能和进化具有决定性作用。

Cell systems Pub Date : 2024-06-19 Epub Date: 2024-06-10 DOI: 10.1016/j.cels.2024.05.005

David Bradley, Chantal Garand, Hugo Belda, Isabelle Gagnon-Arsenault, Moritz Treeck, Sabine Elowe, Christian R Landry

{"title":"The substrate quality of CK2 target sites has a determinant role on their function and evolution.","authors":"David Bradley, Chantal Garand, Hugo Belda, Isabelle Gagnon-Arsenault, Moritz Treeck, Sabine Elowe, Christian R Landry","doi":"10.1016/j.cels.2024.05.005","DOIUrl":"10.1016/j.cels.2024.05.005","url":null,"abstract":"Most biological processes are regulated by signaling modules that bind to short linear motifs. For protein kinases, substrates may have full or only partial matches to the kinase recognition motif, a property known as \"substrate quality.\" However, it is not clear whether differences in substrate quality represent neutral variation or if they have functional consequences. We examine this question for the kinase CK2, which has many fundamental functions. We show that optimal CK2 sites are phosphorylated at maximal stoichiometries and found in many conditions, whereas minimal substrates are more weakly phosphorylated and have regulatory functions. Optimal CK2 sites tend to be more conserved, and substrate quality is often tuned by selection. For intermediate sites, increases or decreases in substrate quality may be deleterious, as we demonstrate for a CK2 substrate at the kinetochore. The results together suggest a strong role for substrate quality in phosphosite function and evolution. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"544-562.e8"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307628","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

How has the AI boom impacted algorithmic biology? 人工智能热潮对算法生物学有何影响？

Cell systems Pub Date : 2024-06-19 DOI: 10.1016/j.cels.2024.05.008

Mona Singh, Cenk Sahinalp, Jianyang Zeng, Wei Vivian Li, Carl Kingsford, Qiangfeng Zhang, Teresa Przytycka, Joshua Welch, Jian Ma, Bonnie Berger

引用次数: 0

To modulate or to skip: De-escalating PARP inhibitor maintenance therapy in ovarian cancer using adaptive therapy. 调节或跳过：利用适应性疗法降低卵巢癌中 PARP 抑制剂维持疗法的等级。

Cell systems Pub Date : 2024-06-19 Epub Date: 2024-05-20 DOI: 10.1016/j.cels.2024.04.003

Maximilian A R Strobl, Alexandra L Martin, Jeffrey West, Jill Gallaher, Mark Robertson-Tessi, Robert Gatenby, Robert Wenham, Philip K Maini, Mehdi Damaghi, Alexander R A Anderson

{"title":"To modulate or to skip: De-escalating PARP inhibitor maintenance therapy in ovarian cancer using adaptive therapy.","authors":"Maximilian A R Strobl, Alexandra L Martin, Jeffrey West, Jill Gallaher, Mark Robertson-Tessi, Robert Gatenby, Robert Wenham, Philip K Maini, Mehdi Damaghi, Alexander R A Anderson","doi":"10.1016/j.cels.2024.04.003","DOIUrl":"10.1016/j.cels.2024.04.003","url":null,"abstract":"Toxicity and emerging drug resistance pose important challenges in poly-adenosine ribose polymerase inhibitor (PARPi) maintenance therapy of ovarian cancer. We propose that adaptive therapy, which dynamically reduces treatment based on the tumor dynamics, might alleviate both issues. Utilizing in vitro time-lapse microscopy and stepwise model selection, we calibrate and validate a differential equation mathematical model, which we leverage to test different plausible adaptive treatment schedules. Our model indicates that adjusting the dosage, rather than skipping treatments, is more effective at reducing drug use while maintaining efficacy due to a delay in cell kill and a diminishing dose-response relationship. In vivo pilot experiments confirm this conclusion. Although our focus is toxicity mitigation, reducing drug use may also delay resistance. This study enhances our understanding of PARPi treatment scheduling and illustrates the first steps in developing adaptive therapies for new treatment settings. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"510-525.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077150","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

Systems genetics of metabolic health in the BXD mouse genetic reference population. BXD 小鼠遗传参考群体代谢健康的系统遗传学。

Cell systems Pub Date : 2024-06-19 Epub Date: 2024-06-11 DOI: 10.1016/j.cels.2024.05.006

Xiaoxu Li, Jean-David Morel, Jonathan Sulc, Alessia De Masi, Amélia Lalou, Giorgia Benegiamo, Johanne Poisson, Yasmine Liu, Giacomo V G Von Alvensleben, Arwen W Gao, Maroun Bou Sleiman, Johan Auwerx

{"title":"Systems genetics of metabolic health in the BXD mouse genetic reference population.","authors":"Xiaoxu Li, Jean-David Morel, Jonathan Sulc, Alessia De Masi, Amélia Lalou, Giorgia Benegiamo, Johanne Poisson, Yasmine Liu, Giacomo V G Von Alvensleben, Arwen W Gao, Maroun Bou Sleiman, Johan Auwerx","doi":"10.1016/j.cels.2024.05.006","DOIUrl":"10.1016/j.cels.2024.05.006","url":null,"abstract":"Susceptibility to metabolic syndrome (MetS) is dependent on genetics, environment, and gene-by-environment interactions, rendering the study of underlying mechanisms challenging. The majority of experiments in model organisms do not incorporate genetic variation and lack specific evaluation criteria for MetS. Here, we derived a continuous metric, the metabolic health score (MHS), based on standard clinical parameters and defined its molecular signatures in the liver and circulation. In human UK Biobank, the MHS associated with MetS status and was predictive of future disease incidence, even in individuals without MetS. Using quantitative trait locus analyses in mice, we found two MHS-associated genetic loci and replicated them in unrelated mouse populations. Through a prioritization scheme in mice and human genetic data, we identified TNKS and MCPH1 as candidates mediating differences in the MHS. Our findings provide insights into the molecular mechanisms sustaining metabolic health across species and uncover likely regulators. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"497-509.e3"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312523","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

Decoupled degradation and translation enables noise modulation by poly(A) tails. 去耦降解和平移可实现多（A）尾噪音调制。

Cell systems Pub Date : 2024-06-19 DOI: 10.1016/j.cels.2024.05.004

Carmen Grandi, Martin Emmaneel, Frank H T Nelissen, Laura W M Roosenboom, Yoanna Petrova, Omnia Elzokla, Maike M K Hansen

{"title":"Decoupled degradation and translation enables noise modulation by poly(A) tails.","authors":"Carmen Grandi, Martin Emmaneel, Frank H T Nelissen, Laura W M Roosenboom, Yoanna Petrova, Omnia Elzokla, Maike M K Hansen","doi":"10.1016/j.cels.2024.05.004","DOIUrl":"https://doi.org/10.1016/j.cels.2024.05.004","url":null,"abstract":"Poly(A) tails are crucial for mRNA translation and degradation, but the exact relationship between tail length and mRNA kinetics remains unclear. Here, we employ a small library of identical mRNAs that differ only in their poly(A)-tail length to examine their behavior in human embryonic kidney cells. We find that tail length strongly correlates with mRNA degradation rates but is decoupled from translation. Interestingly, an optimal tail length of ∼100 nt displays the highest translation rate, which is identical to the average endogenous tail length measured by nanopore sequencing. Furthermore, poly(A)-tail length variability-a feature of endogenous mRNAs-impacts translation efficiency but not mRNA degradation rates. Stochastic modeling combined with single-cell tracking reveals that poly(A) tails provide cells with an independent handle to tune gene expression fluctuations by decoupling mRNA degradation and translation. Together, this work contributes to the basic understanding of gene expression regulation and has potential applications in nucleic acid therapeutics.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 6","pages":"526-543.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433660","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

Accurate single-molecule spot detection for image-based spatial transcriptomics with weakly supervised deep learning. 利用弱监督深度学习为基于图像的空间转录组学提供精确的单分子点检测。

Cell systems Pub Date : 2024-05-15 DOI: 10.1016/j.cels.2024.04.006

Emily Laubscher, Xuefei Wang, Nitzan Razin, Tom Dougherty, Rosalind J Xu, Lincoln Ombelets, Edward Pao, William Graf, Jeffrey R Moffitt, Yisong Yue, David Van Valen

引用次数: 0

Multilevel relations among plankton stitched together with an eco-evolutionary needle. 用生态进化针缝合浮游生物之间的多层次关系。

Cell systems Pub Date : 2024-05-15 DOI: 10.1016/j.cels.2024.04.007

Van M Savage

引用次数: 0