Cell Systems最新文献_第7页

Transcriptional activators in the early Drosophila embryo perform different kinetic roles. 转录激活因子在果蝇早期胚胎中发挥着不同的动力学作用。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-04-19 DOI: 10.1016/j.cels.2023.03.006

Timothy T Harden, Ben J Vincent, Angela H DePace

{"title":"Transcriptional activators in the early Drosophila embryo perform different kinetic roles.","authors":"Timothy T Harden, Ben J Vincent, Angela H DePace","doi":"10.1016/j.cels.2023.03.006","DOIUrl":"https://doi.org/10.1016/j.cels.2023.03.006","url":null,"abstract":"Combinatorial regulation of gene expression by transcription factors (TFs) may in part arise from kinetic synergy-wherein TFs regulate different steps in the transcription cycle. Kinetic synergy requires that TFs play distinguishable kinetic roles. Here, we used live imaging to determine the kinetic roles of three TFs that activate transcription in the Drosophila embryo-Zelda, Bicoid, and Stat92E-by introducing their binding sites into the even-skipped stripe 2 enhancer. These TFs influence different sets of kinetic parameters, and their influence can change over time. All three TFs increased the fraction of transcriptionally active nuclei; Zelda also shortened the first-passage time into transcription and regulated the interval between transcription events. Stat92E also increased the lifetimes of active transcription. Different TFs can therefore play distinct kinetic roles in activating the transcription. This has consequences for understanding the composition and flexibility of regulatory DNA sequences and the biochemical function of TFs. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 4","pages":"258-272.e4"},"PeriodicalIF":9.3,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473017/pdf/nihms-1919371.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10496130","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

Entropic analysis of antigen-specific CDR3 domains identifies essential binding motifs shared by CDR3s with different antigen specificities. 抗原特异性 CDR3 结构域的熵分析确定了不同抗原特异性 CDR3 共享的基本结合基序。

IF 9 1区生物学

Cell Systems Pub Date : 2023-04-19 Epub Date: 2023-03-30 DOI: 10.1016/j.cels.2023.03.001

Alexander M Xu, William Chour, Diana C DeLucia, Yapeng Su, Ana Jimena Pavlovitch-Bedzyk, Rachel Ng, Yusuf Rasheed, Mark M Davis, John K Lee, James R Heath

{"title":"Entropic analysis of antigen-specific CDR3 domains identifies essential binding motifs shared by CDR3s with different antigen specificities.","authors":"Alexander M Xu, William Chour, Diana C DeLucia, Yapeng Su, Ana Jimena Pavlovitch-Bedzyk, Rachel Ng, Yusuf Rasheed, Mark M Davis, John K Lee, James R Heath","doi":"10.1016/j.cels.2023.03.001","DOIUrl":"10.1016/j.cels.2023.03.001","url":null,"abstract":"Antigen-specific T cell receptor (TCR) sequences can have prognostic, predictive, and therapeutic value, but decoding the specificity of TCR recognition remains challenging. Unlike DNA strands that base pair, TCRs bind to their targets with different orientations and different lengths, which complicates comparisons. We present scanning parametrized by normalized TCR length (SPAN-TCR) to analyze antigen-specific TCR CDR3 sequences and identify patterns driving TCR-pMHC specificity. Using entropic analysis, SPAN-TCR identifies 2-mer motifs that decrease the diversity (entropy) of CDR3s. These motifs are the most common patterns that can predict CDR3 composition, and we identify \"essential\" motifs that decrease entropy in the same CDR3 α or β chain containing the 2-mer, and \"super-essential\" motifs that decrease entropy in both chains. Molecular dynamics analysis further suggests that these motifs may play important roles in binding. We then employ SPAN-TCR to resolve similarities in TCR repertoires against different antigens using public databases of TCR sequences.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 4","pages":"273-284.e5"},"PeriodicalIF":9.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10355346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9895818","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

Uncovering the spatial landscape of molecular interactions within the tumor microenvironment through latent spaces. 通过潜伏空间揭示肿瘤微环境中分子相互作用的空间景观。

IF 9 1区生物学

Cell Systems Pub Date : 2023-04-19 DOI: 10.1016/j.cels.2023.03.004

Atul Deshpande, Melanie Loth, Dimitrios N Sidiropoulos, Shuming Zhang, Long Yuan, Alexander T F Bell, Qingfeng Zhu, Won Jin Ho, Cesar Santa-Maria, Daniele M Gilkes, Stephen R Williams, Cedric R Uytingco, Jennifer Chew, Andrej Hartnett, Zachary W Bent, Alexander V Favorov, Aleksander S Popel, Mark Yarchoan, Ashley Kiemen, Pei-Hsun Wu, Kohei Fujikura, Denis Wirtz, Laura D Wood, Lei Zheng, Elizabeth M Jaffee, Robert A Anders, Ludmila Danilova, Genevieve Stein-O'Brien, Luciane T Kagohara, Elana J Fertig

{"title":"Uncovering the spatial landscape of molecular interactions within the tumor microenvironment through latent spaces.","authors":"Atul Deshpande, Melanie Loth, Dimitrios N Sidiropoulos, Shuming Zhang, Long Yuan, Alexander T F Bell, Qingfeng Zhu, Won Jin Ho, Cesar Santa-Maria, Daniele M Gilkes, Stephen R Williams, Cedric R Uytingco, Jennifer Chew, Andrej Hartnett, Zachary W Bent, Alexander V Favorov, Aleksander S Popel, Mark Yarchoan, Ashley Kiemen, Pei-Hsun Wu, Kohei Fujikura, Denis Wirtz, Laura D Wood, Lei Zheng, Elizabeth M Jaffee, Robert A Anders, Ludmila Danilova, Genevieve Stein-O'Brien, Luciane T Kagohara, Elana J Fertig","doi":"10.1016/j.cels.2023.03.004","DOIUrl":"10.1016/j.cels.2023.03.004","url":null,"abstract":"Recent advances in spatial transcriptomics (STs) enable gene expression measurements from a tissue sample while retaining its spatial context. This technology enables unprecedented in situ resolution of the regulatory pathways that underlie the heterogeneity in the tumor as well as the tumor microenvironment (TME). The direct characterization of cellular co-localization with spatial technologies facilities quantification of the molecular changes resulting from direct cell-cell interaction, as it occurs in tumor-immune interactions. We present SpaceMarkers, a bioinformatics algorithm to infer molecular changes from cell-cell interactions from latent space analysis of ST data. We apply this approach to infer the molecular changes from tumor-immune interactions in Visium spatial transcriptomics data of metastasis, invasive and precursor lesions, and immunotherapy treatment. Further transfer learning in matched scRNA-seq data enabled further quantification of the specific cell types in which SpaceMarkers are enriched. Altogether, SpaceMarkers can identify the location and context-specific molecular interactions within the TME from ST data.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 4","pages":"285-301.e4"},"PeriodicalIF":9.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044262","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

Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation. 癌症细胞集体行为的建模：跨学科对话的视角。

IF 9 1区生物学

Cell Systems Pub Date : 2023-04-19 DOI: 10.1016/j.cels.2023.03.002

Frederick R Adler, Alexander R A Anderson, Abhinav Bhushan, Paul Bogdan, Jose Javier Bravo-Cordero, Amy Brock, Yun Chen, Edna Cukierman, Kathleen E DelGiorno, Gerald V Denis, Meghan C Ferrall-Fairbanks, Zev Jordan Gartner, Ronald N Germain, Deborah M Gordon, Ginger Hunter, Mohit Kumar Jolly, Loukia Georgiou Karacosta, Karthikeyan Mythreye, Parag Katira, Rajan P Kulkarni, Matthew L Kutys, Arthur D Lander, Ashley M Laughney, Herbert Levine, Emil Lou, Pedro R Lowenstein, Kristyn S Masters, Dana Pe'er, Shelly R Peyton, Manu O Platt, Jeremy E Purvis, Gerald Quon, Jennifer K Richer, Nicole C Riddle, Analiz Rodriguez, Joshua C Snyder, Gregory Lee Szeto, Claire J Tomlin, Itai Yanai, Ioannis K Zervantonakis, Hannah Dueck

{"title":"Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation.","authors":"Frederick R Adler, Alexander R A Anderson, Abhinav Bhushan, Paul Bogdan, Jose Javier Bravo-Cordero, Amy Brock, Yun Chen, Edna Cukierman, Kathleen E DelGiorno, Gerald V Denis, Meghan C Ferrall-Fairbanks, Zev Jordan Gartner, Ronald N Germain, Deborah M Gordon, Ginger Hunter, Mohit Kumar Jolly, Loukia Georgiou Karacosta, Karthikeyan Mythreye, Parag Katira, Rajan P Kulkarni, Matthew L Kutys, Arthur D Lander, Ashley M Laughney, Herbert Levine, Emil Lou, Pedro R Lowenstein, Kristyn S Masters, Dana Pe'er, Shelly R Peyton, Manu O Platt, Jeremy E Purvis, Gerald Quon, Jennifer K Richer, Nicole C Riddle, Analiz Rodriguez, Joshua C Snyder, Gregory Lee Szeto, Claire J Tomlin, Itai Yanai, Ioannis K Zervantonakis, Hannah Dueck","doi":"10.1016/j.cels.2023.03.002","DOIUrl":"10.1016/j.cels.2023.03.002","url":null,"abstract":"Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approaches. Here, we summarize an interdisciplinary discussion on multicellular behavior in cancer, draw lessons from other scientific disciplines, and identify future directions.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 4","pages":"252-257"},"PeriodicalIF":9.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10760508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522098","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

Transcriptional kinetic synergy: A complex landscape revealed by integrating modeling and synthetic biology. 转录动力学协同作用:一个复杂的景观揭示了整合建模和合成生物学。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-04-19 DOI: 10.1016/j.cels.2023.02.003

Rosa Martinez-Corral, Minhee Park, Kelly M Biette, Dhana Friedrich, Clarissa Scholes, Ahmad S Khalil, Jeremy Gunawardena, Angela H DePace

{"title":"Transcriptional kinetic synergy: A complex landscape revealed by integrating modeling and synthetic biology.","authors":"Rosa Martinez-Corral, Minhee Park, Kelly M Biette, Dhana Friedrich, Clarissa Scholes, Ahmad S Khalil, Jeremy Gunawardena, Angela H DePace","doi":"10.1016/j.cels.2023.02.003","DOIUrl":"https://doi.org/10.1016/j.cels.2023.02.003","url":null,"abstract":"Transcription factors (TFs) control gene expression, often acting synergistically. Classical thermodynamic models offer a biophysical explanation for synergy based on binding cooperativity and regulated recruitment of RNA polymerase. Because transcription requires polymerase to transition through multiple states, recent work suggests that \"kinetic synergy\" can arise through TFs acting on distinct steps of the transcription cycle. These types of synergy are not mutually exclusive and are difficult to disentangle conceptually and experimentally. Here, we model and build a synthetic circuit in which TFs bind to a single shared site on DNA, such that TFs cannot synergize by simultaneous binding. We model mRNA production as a function of both TF binding and regulation of the transcription cycle, revealing a complex landscape dependent on TF concentration, DNA binding affinity, and regulatory activity. We use synthetic TFs to confirm that the transcription cycle must be integrated with recruitment for a quantitative understanding of gene regulation.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 4","pages":"324-339.e7"},"PeriodicalIF":9.3,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/6d/nihms-1894994.PMC10472254.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10197841","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

scTenifoldXct: A semi-supervised method for predicting cell-cell interactions and mapping cellular communication graphs. scTenifoldXct：预测细胞间相互作用和绘制细胞通讯图的半监督方法

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-04-19 Epub Date: 2023-02-13 DOI: 10.1016/j.cels.2023.01.004

Yongjian Yang, Guanxun Li, Yan Zhong, Qian Xu, Yu-Te Lin, Cristhian Roman-Vicharra, Robert S Chapkin, James J Cai

{"title":"scTenifoldXct: A semi-supervised method for predicting cell-cell interactions and mapping cellular communication graphs.","authors":"Yongjian Yang, Guanxun Li, Yan Zhong, Qian Xu, Yu-Te Lin, Cristhian Roman-Vicharra, Robert S Chapkin, James J Cai","doi":"10.1016/j.cels.2023.01.004","DOIUrl":"10.1016/j.cels.2023.01.004","url":null,"abstract":"We present scTenifoldXct, a semi-supervised computational tool for detecting ligand-receptor (LR)-mediated cell-cell interactions and mapping cellular communication graphs. Our method is based on manifold alignment, using LR pairs as inter-data correspondences to embed ligand and receptor genes expressed in interacting cells into a unified latent space. Neural networks are employed to minimize the distance between corresponding genes while preserving the structure of gene regression networks. We apply scTenifoldXct to real datasets for testing and demonstrate that our method detects interactions with high consistency compared with other methods. More importantly, scTenifoldXct uncovers weak but biologically relevant interactions overlooked by other methods. We also demonstrate how scTenifoldXct can be used to compare different samples, such as healthy vs. diseased and wild type vs. knockout, to identify differential interactions, thereby revealing functional implications associated with changes in cellular communication status.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 4","pages":"302-311.e4"},"PeriodicalIF":9.3,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9519439","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

Genes enriched in A/T-ending codons are co-regulated and conserved across mammals. 富含A/ t末端密码子的基因在哺乳动物中是共同调控和保守的。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-04-19 DOI: 10.1016/j.cels.2023.02.002

Hannah Benisty, Xavier Hernandez-Alias, Marc Weber, Miquel Anglada-Girotto, Federica Mantica, Leandro Radusky, Gökçe Senger, Ferriol Calvet, Donate Weghorn, Manuel Irimia, Martin H Schaefer, Luis Serrano

{"title":"Genes enriched in A/T-ending codons are co-regulated and conserved across mammals.","authors":"Hannah Benisty, Xavier Hernandez-Alias, Marc Weber, Miquel Anglada-Girotto, Federica Mantica, Leandro Radusky, Gökçe Senger, Ferriol Calvet, Donate Weghorn, Manuel Irimia, Martin H Schaefer, Luis Serrano","doi":"10.1016/j.cels.2023.02.002","DOIUrl":"https://doi.org/10.1016/j.cels.2023.02.002","url":null,"abstract":"Codon usage influences gene expression distinctly depending on the cell context. Yet, the importance of codon bias in the simultaneous turnover of specific groups of protein-coding genes remains to be investigated. Here, we find that genes enriched in A/T-ending codons are expressed more coordinately in general and across tissues and development than those enriched in G/C-ending codons. tRNA abundance measurements indicate that this coordination is linked to the expression changes of tRNA isoacceptors reading A/T-ending codons. Genes with similar codon composition are more likely to be part of the same protein complex, especially for genes with A/T-ending codons. The codon preferences of genes with A/T-ending codons are conserved among mammals and other vertebrates. We suggest that this orchestration contributes to tissue-specific and ontogenetic-specific expression, which can facilitate, for instance, timely protein complex formation.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 4","pages":"312-323.e3"},"PeriodicalIF":9.3,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518856","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: 3

A complete allosteric map of a GTPase switch in its native cellular network. 原生细胞网络中 GTPase 开关的完整异构图。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-03-15 Epub Date: 2023-02-17 DOI: 10.1016/j.cels.2023.01.003

Christopher J P Mathy, Parul Mishra, Julia M Flynn, Tina Perica, David Mavor, Daniel N A Bolon, Tanja Kortemme

{"title":"A complete allosteric map of a GTPase switch in its native cellular network.","authors":"Christopher J P Mathy, Parul Mishra, Julia M Flynn, Tina Perica, David Mavor, Daniel N A Bolon, Tanja Kortemme","doi":"10.1016/j.cels.2023.01.003","DOIUrl":"10.1016/j.cels.2023.01.003","url":null,"abstract":"Allosteric regulation is central to protein function in cellular networks. A fundamental open question is whether cellular regulation of allosteric proteins occurs only at a few defined positions or at many sites distributed throughout the structure. Here, we probe the regulation of GTPases-protein switches that control signaling through regulated conformational cycling-at residue-level resolution by deep mutagenesis in the native biological network. For the GTPase Gsp1/Ran, we find that 28% of the 4,315 assayed mutations show pronounced gain-of-function responses. Twenty of the sixty positions enriched for gain-of-function mutations are outside the canonical GTPase active site switch regions. Kinetic analysis shows that these distal sites are allosterically coupled to the active site. We conclude that the GTPase switch mechanism is broadly sensitive to cellular allosteric regulation. Our systematic discovery of new regulatory sites provides a functional map to interrogate and target GTPases controlling many essential biological processes.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 3","pages":"237-246.e7"},"PeriodicalIF":9.3,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10173951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9819255","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

A novel network approach to multiscale biological regulation. 多尺度生物调控的新网络方法。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-03-15 DOI: 10.1016/j.cels.2023.02.004

Guido Gigante, Alessandro Giuliani, Maurizio Mattia

引用次数: 2

Undersampling and the inference of coevolution in proteins. 蛋白质中的欠采样和共同进化推论

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-03-15 Epub Date: 2023-01-23 DOI: 10.1016/j.cels.2022.12.013

Yaakov Kleeorin, William P Russ, Olivier Rivoire, Rama Ranganathan

引用次数: 0