Cell Systems最新文献_第8页

Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient. 最小合成增强子揭示了通过形态发生梯度控制转录参与的概率及其时间。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-03-15 Epub Date: 2023-01-24 DOI: 10.1016/j.cels.2022.12.008

Simon Alamos, Armando Reimer, Clay Westrum, Meghan A Turner, Paul Talledo, Jiaxi Zhao, Emma Luu, Hernan G Garcia

{"title":"Minimal synthetic enhancers reveal control of the probability of transcriptional engagement and its timing by a morphogen gradient.","authors":"Simon Alamos, Armando Reimer, Clay Westrum, Meghan A Turner, Paul Talledo, Jiaxi Zhao, Emma Luu, Hernan G Garcia","doi":"10.1016/j.cels.2022.12.008","DOIUrl":"10.1016/j.cels.2022.12.008","url":null,"abstract":"How enhancers interpret morphogen gradients to generate gene expression patterns is a central question in developmental biology. Recent studies have proposed that enhancers can dictate whether, when, and at what rate promoters engage in transcription, but the complexity of endogenous enhancers calls for theoretical models with too many free parameters to quantitatively dissect these regulatory strategies. To overcome this limitation, we established a minimal promoter-proximal synthetic enhancer in embryos of Drosophila melanogaster. Here, a gradient of the Dorsal activator is read by a single Dorsal DNA binding site. Using live imaging to quantify transcriptional activity, we found that a single binding site can regulate whether promoters engage in transcription in a concentration-dependent manner. By modulating the binding-site affinity, we determined that a gene's decision to transcribe and its transcriptional onset time can be explained by a simple model where the promoter traverses multiple kinetic barriers before transcription can ensue.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 3","pages":"220-236.e3"},"PeriodicalIF":9.3,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9346864","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

Quantifying stimulus-response specificity to probe the functional state of macrophages. 量化刺激-反应特异性，探究巨噬细胞的功能状态。

IF 9 1区生物学

Cell Systems Pub Date : 2023-03-15 Epub Date: 2023-01-18 DOI: 10.1016/j.cels.2022.12.012

Katherine M Sheu, Aditya A Guru, Alexander Hoffmann

{"title":"Quantifying stimulus-response specificity to probe the functional state of macrophages.","authors":"Katherine M Sheu, Aditya A Guru, Alexander Hoffmann","doi":"10.1016/j.cels.2022.12.012","DOIUrl":"10.1016/j.cels.2022.12.012","url":null,"abstract":"Immune sentinel macrophages initiate responses to pathogens via hundreds of immune response genes. Each immune threat demands a tailored response, suggesting that the capacity for stimulus-specific gene expression is a key functional hallmark of healthy macrophages. To quantify this property, termed \"stimulus-response specificity\" (SRS), we developed a single-cell experimental workflow and analytical approaches based on information theory and machine learning. We found that the response specificity of macrophages is driven by combinations of specific immune genes that show low cell-to-cell heterogeneity and are targets of separate signaling pathways. The \"response specificity profile,\" a systematic comparison of multiple stimulus-response distributions, was distinctly altered by polarizing cytokines, and it enabled an assessment of the functional state of macrophages. Indeed, the response specificity profile of peritoneal macrophages from old and obese mice showed characteristic differences, suggesting that SRS may be a basis for measuring the functional state of innate immune cells. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 3","pages":"180-195.e5"},"PeriodicalIF":9.0,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9171967","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

Leading edge competition promotes context-dependent responses to receptor inputs to resolve directional dilemmas in neutrophil migration. 前缘竞争促进了对受体输入的情境依赖性反应，以解决中性粒细胞迁移中的定向困境。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-03-15 Epub Date: 2023-02-23 DOI: 10.1016/j.cels.2023.02.001

Amalia Hadjitheodorou, George R R Bell, Felix Ellett, Daniel Irimia, Robert Tibshirani, Sean R Collins, Julie A Theriot

{"title":"Leading edge competition promotes context-dependent responses to receptor inputs to resolve directional dilemmas in neutrophil migration.","authors":"Amalia Hadjitheodorou, George R R Bell, Felix Ellett, Daniel Irimia, Robert Tibshirani, Sean R Collins, Julie A Theriot","doi":"10.1016/j.cels.2023.02.001","DOIUrl":"10.1016/j.cels.2023.02.001","url":null,"abstract":"Maintaining persistent migration in complex environments is critical for neutrophils to reach infection sites. Neutrophils avoid getting trapped, even when obstacles split their front into multiple leading edges. How they re-establish polarity to move productively while incorporating receptor inputs under such conditions remains unclear. Here, we challenge chemotaxing HL60 neutrophil-like cells with symmetric bifurcating microfluidic channels to probe cell-intrinsic processes during the resolution of competing fronts. Using supervised statistical learning, we demonstrate that cells commit to one leading edge late in the process, rather than amplifying structural asymmetries or early fluctuations. Using optogenetic tools, we show that receptor inputs only bias the decision similarly late, once mechanical stretching begins to weaken each front. Finally, a retracting edge commits to retraction, with ROCK limiting sensitivity to receptor inputs until the retraction completes. Collectively, our results suggest that cell edges locally adopt highly stable protrusion/retraction programs that are modulated by mechanical feedback.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"14 3","pages":"196-209.e6"},"PeriodicalIF":9.3,"publicationDate":"2023-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/97/10/nihms-1889296.PMC10150694.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9381784","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

Metabolic models of human gut microbiota: Advances and challenges. 人类肠道微生物群的代谢模型:进展与挑战。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-02-15 DOI: 10.1016/j.cels.2022.11.002

Daniel Rios Garza, Didier Gonze, Haris Zafeiropoulos, Bin Liu, Karoline Faust

引用次数: 2

Pitfalls of genotyping microbial communities with rapidly growing genome collections. 利用快速增长的基因组集合对微生物群落进行基因分型的陷阱。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-02-15 Epub Date: 2023-01-18 DOI: 10.1016/j.cels.2022.12.007

Chunyu Zhao, Zhou Jason Shi, Katherine S Pollard

引用次数: 0

What is the key challenge in engineering microbiomes? 工程微生物组的关键挑战是什么?

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-02-15 DOI: 10.1016/j.cels.2023.01.002

Ophelia S Venturelli, Harris H Wang, Sylvie Estrela, Kerwyn Casey Huang, Rodrigo Ledesma-Amaro, Alex J H Fedorec, Bärbel Stecher, Christopher E Lawson, Amir Zarrinpar, Chun-Jun Guo, Orkun S Soyer

引用次数: 1

Spatial self-organization of metabolism in microbial systems: A matter of enzymes and chemicals. 微生物系统中新陈代谢的空间自组织:酶和化学物质的问题。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-02-15 DOI: 10.1016/j.cels.2022.12.009

Alma Dal Co, Martin Ackermann, Simon van Vliet

引用次数: 2

Controlling the human microbiome. 控制人类微生物群

IF 9 1区生物学

Cell Systems Pub Date : 2023-02-15 DOI: 10.1016/j.cels.2022.12.010

Yang-Yu Liu

引用次数: 0

What do you most want to understand about how collective features emerge in microbial communities? 关于微生物群落的集体特征是如何出现的，你最想了解的是什么?

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-02-15 DOI: 10.1016/j.cels.2023.01.001

Daniel Segrè, Sara Mitri, Wenying Shou, Gürol M Süel, Itzhak Mizrahi, Libusha Kelly, María Rebolleda-Gómez, Christoph Ratzke, C Brandon Ogbunugafor, Julia A Schwartzman, Sergey Kryazhimskiy, Gabriel E Leventhal, Christian Kost, Thomas Bell

引用次数: 2

The community-function landscape of microbial consortia. 微生物群落功能景观。

IF 9.3 1区生物学

Cell Systems Pub Date : 2023-02-15 DOI: 10.1016/j.cels.2022.12.011

Alvaro Sanchez, Djordje Bajic, Juan Diaz-Colunga, Abigail Skwara, Jean C C Vila, Seppe Kuehn

引用次数: 19