Cell systems最新文献_第6页

Global transcription regulation revealed from dynamical correlations in time-resolved single-cell RNA sequencing. 从时间分辨单细胞 RNA 测序的动态相关性中揭示全球转录调控。

Cell systems Pub Date : 2024-08-21 Epub Date: 2024-08-08 DOI: 10.1016/j.cels.2024.07.002

Dimitris Volteras, Vahid Shahrezaei, Philipp Thomas

{"title":"Global transcription regulation revealed from dynamical correlations in time-resolved single-cell RNA sequencing.","authors":"Dimitris Volteras, Vahid Shahrezaei, Philipp Thomas","doi":"10.1016/j.cels.2024.07.002","DOIUrl":"10.1016/j.cels.2024.07.002","url":null,"abstract":"Single-cell transcriptomics reveals significant variations in transcriptional activity across cells. Yet, it remains challenging to identify mechanisms of transcription dynamics from static snapshots. It is thus still unknown what drives global transcription dynamics in single cells. We present a stochastic model of gene expression with cell size- and cell cycle-dependent rates in growing and dividing cells that harnesses temporal dimensions of single-cell RNA sequencing through metabolic labeling protocols and cel lcycle reporters. We develop a parallel and highly scalable approximate Bayesian computation method that corrects for technical variation and accurately quantifies absolute burst frequency, burst size, and degradation rate along the cell cycle at a transcriptome-wide scale. Using Bayesian model selection, we reveal scaling between transcription rates and cell size and unveil waves of gene regulation across the cell cycle-dependent transcriptome. Our study shows that stochastic modeling of dynamical correlations identifies global mechanisms of transcription regulation. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"694-708.e12"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914806","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

Evaluation of Kernfeld et al.: Toward best practices for tackling false positives in regulatory network inference. 对 Kernfeld 等人的评估：解决调控网络推断中假阳性问题的最佳实践。

Cell systems Pub Date : 2024-08-21 DOI: 10.1016/j.cels.2024.07.009

Anthony Gitter

引用次数: 0

Transcriptome data are insufficient to control false discoveries in regulatory network inference. 转录组数据不足以控制调控网络推断中的错误发现。

Cell systems Pub Date : 2024-08-21 DOI: 10.1016/j.cels.2024.07.006

Eric Kernfeld, Rebecca Keener, Patrick Cahan, Alexis Battle

{"title":"Transcriptome data are insufficient to control false discoveries in regulatory network inference.","authors":"Eric Kernfeld, Rebecca Keener, Patrick Cahan, Alexis Battle","doi":"10.1016/j.cels.2024.07.006","DOIUrl":"10.1016/j.cels.2024.07.006","url":null,"abstract":"Inference of causal transcriptional regulatory networks (TRNs) from transcriptomic data suffers notoriously from false positives. Approaches to control the false discovery rate (FDR), for example, via permutation, bootstrapping, or multivariate Gaussian distributions, suffer from several complications: difficulty in distinguishing direct from indirect regulation, nonlinear effects, and causal structure inference requiring \"causal sufficiency,\" meaning experiments that are free of any unmeasured, confounding variables. Here, we use a recently developed statistical framework, model-X knockoffs, to control the FDR while accounting for indirect effects, nonlinear dose-response, and user-provided covariates. We adjust the procedure to estimate the FDR correctly even when measured against incomplete gold standards. However, benchmarking against chromatin immunoprecipitation (ChIP) and other gold standards reveals higher observed than reported FDR. This indicates that unmeasured confounding is a major driver of FDR in TRN inference. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 8","pages":"709-724.e13"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11642480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038015","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

Enhanced cellular longevity arising from environmental fluctuations. 环境波动导致细胞寿命延长。

Cell systems Pub Date : 2024-08-21 DOI: 10.1016/j.cels.2024.07.007

Yuting Liu, Zhen Zhou, Hetian Su, Songlin Wu, Gavin Ni, Alex Zhang, Lev S Tsimring, Jeff Hasty, Nan Hao

引用次数: 0

Brain dynamics supported by a hierarchy of complex correlation patterns defining a robust functional architecture. 复杂相关模式的层次结构支持大脑动态，定义了一个强大的功能架构。

Cell systems Pub Date : 2024-08-21 Epub Date: 2024-08-13 DOI: 10.1016/j.cels.2024.07.003

Levente Varga, Vasile V Moca, Botond Molnár, Laura Perez-Cervera, Mohamed Kotb Selim, Antonio Díaz-Parra, David Moratal, Balázs Péntek, Wolfgang H Sommer, Raul C Mureșan, Santiago Canals, Maria Ercsey-Ravasz

{"title":"Brain dynamics supported by a hierarchy of complex correlation patterns defining a robust functional architecture.","authors":"Levente Varga, Vasile V Moca, Botond Molnár, Laura Perez-Cervera, Mohamed Kotb Selim, Antonio Díaz-Parra, David Moratal, Balázs Péntek, Wolfgang H Sommer, Raul C Mureșan, Santiago Canals, Maria Ercsey-Ravasz","doi":"10.1016/j.cels.2024.07.003","DOIUrl":"10.1016/j.cels.2024.07.003","url":null,"abstract":"Functional magnetic resonance imaging (fMRI) provides insights into cognitive processes with significant clinical potential. However, delays in brain region communication and dynamic variations are often overlooked in functional network studies. We demonstrate that networks extracted from fMRI cross-correlation matrices, considering time lags between signals, show remarkable reliability when focusing on statistical distributions of network properties. This reveals a robust brain functional connectivity pattern, featuring a sparse backbone of strong 0-lag correlations and weaker links capturing coordination at various time delays. This dynamic yet stable network architecture is consistent across rats, marmosets, and humans, as well as in electroencephalogram (EEG) data, indicating potential universality in brain dynamics. Second-order properties of the dynamic functional network reveal a remarkably stable hierarchy of functional correlations in both group-level comparisons and test-retest analyses. Validation using alcohol use disorder fMRI data uncovers broader shifts in network properties than previously reported, demonstrating the potential of this method for identifying disease biomarkers.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"770-786.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984113","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 identification of transcriptional activation domains from non-transcription factor proteins in plants and yeast. 系统鉴定植物和酵母中非转录因子蛋白的转录激活结构域。

Cell systems Pub Date : 2024-07-17 Epub Date: 2024-06-11 DOI: 10.1016/j.cels.2024.05.007

Niklas F C Hummel, Kasey Markel, Jordan Stefani, Max V Staller, Patrick M Shih

{"title":"Systematic identification of transcriptional activation domains from non-transcription factor proteins in plants and yeast.","authors":"Niklas F C Hummel, Kasey Markel, Jordan Stefani, Max V Staller, Patrick M Shih","doi":"10.1016/j.cels.2024.05.007","DOIUrl":"10.1016/j.cels.2024.05.007","url":null,"abstract":"Transcription factors can promote gene expression through activation domains. Whole-genome screens have systematically mapped activation domains in transcription factors but not in non-transcription factor proteins (e.g., chromatin regulators and coactivators). To fill this knowledge gap, we employed the activation domain predictor PADDLE to analyze the proteomes of Arabidopsis thaliana and Saccharomyces cerevisiae. We screened 18,000 predicted activation domains from >800 non-transcription factor genes in both species, confirming that 89% of candidate proteins contain active fragments. Our work enables the annotation of hundreds of nuclear proteins as putative coactivators, many of which have never been ascribed any function in plants. Analysis of peptide sequence compositions reveals how the distribution of key amino acids dictates activity. Finally, we validated short, \"universal\" activation domains with comparable performance to state-of-the-art activation domains used for genome engineering. Our approach enables the genome-wide discovery and annotation of activation domains that can function across diverse eukaryotes.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"662-672.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312522","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

SEMPER: Stoichiometric expression of mRNA polycistrons by eukaryotic ribosomes for compact, ratio-tunable multi-gene expression. SEMPER：真核核糖体对 mRNA 多单元的定量表达，实现紧凑、比例可调的多基因表达。

Cell systems Pub Date : 2024-07-17 Epub Date: 2024-07-05 DOI: 10.1016/j.cels.2024.06.001

Mengtong Duan, Ishaan Dev, Andrew Lu, Goar Ayrapetyan, Mei Yi You, Mikhail G Shapiro

{"title":"SEMPER: Stoichiometric expression of mRNA polycistrons by eukaryotic ribosomes for compact, ratio-tunable multi-gene expression.","authors":"Mengtong Duan, Ishaan Dev, Andrew Lu, Goar Ayrapetyan, Mei Yi You, Mikhail G Shapiro","doi":"10.1016/j.cels.2024.06.001","DOIUrl":"10.1016/j.cels.2024.06.001","url":null,"abstract":"Here, we present a method for expressing multiple open reading frames (ORFs) from single transcripts using the leaky scanning model of translation initiation. In this approach termed \"stoichiometric expression of mRNA polycistrons by eukaryotic ribosomes\" (SEMPER), adjacent ORFs are translated from a single mRNA at tunable ratios determined by their order in the sequence and the strength of their translation initiation sites. We validate this approach by expressing up to three fluorescent proteins from one plasmid in two different cell lines. We then use it to encode a stoichiometrically tuned polycistronic construct encoding gas vesicle acoustic reporter genes that enables efficient formation of the multi-protein complex while minimizing cellular toxicity. We also demonstrate that SEMPER enables polycistronic expression of recombinant monoclonal antibodies from plasmid DNA and of two fluorescent proteins from single mRNAs made through in vitro transcription. Finally, we provide a probabilistic model to elucidate the mechanisms underlying SEMPER. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"597-609.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545640","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

Highly parallel production of designer organoids by mosaic patterning of progenitors. 通过对祖细胞进行镶嵌图案化，高度并行地生产出设计器官。

Cell systems Pub Date : 2024-07-17 Epub Date: 2024-07-08 DOI: 10.1016/j.cels.2024.06.004

Catherine M Porter, Grace C Qian, Samuel H Grindel, Alex J Hughes

{"title":"Highly parallel production of designer organoids by mosaic patterning of progenitors.","authors":"Catherine M Porter, Grace C Qian, Samuel H Grindel, Alex J Hughes","doi":"10.1016/j.cels.2024.06.004","DOIUrl":"10.1016/j.cels.2024.06.004","url":null,"abstract":"Organoids derived from human stem cells are a promising approach for disease modeling, regenerative medicine, and fundamental research. However, organoid variability and limited control over morphological outcomes remain as challenges. One open question is the extent to which engineering control over culture conditions can guide organoids to specific compositions. Here, we extend a DNA \"velcro\" cell patterning approach, precisely controlling the number and ratio of human induced pluripotent stem cell-derived progenitors contributing to nephron progenitor (NP) organoids and mosaic NP/ureteric bud (UB) tip cell organoids within arrays of microwells. We demonstrate long-term control over organoid size and morphology, decoupled from geometric constraints. We then show emergent trends in organoid tissue proportions that depend on initial progenitor cell composition. These include higher nephron and stromal cell representation in mosaic NP/UB organoids vs. NP-only organoids and a \"goldilocks\" initial cell ratio in mosaic organoids that optimizes the formation of proximal tubule structures.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"649-661.e9"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565354","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

Signal integration and adaptive sensory diversity tuning in Escherichia coli chemotaxis. 大肠杆菌趋化过程中的信号整合与适应性感觉多样性调整

Cell systems Pub Date : 2024-07-17 Epub Date: 2024-07-08 DOI: 10.1016/j.cels.2024.06.003

Jeremy Philippe Moore, Keita Kamino, Rafaela Kottou, Thomas S Shimizu, Thierry Emonet

引用次数: 0

The unreasonable effectiveness of equilibrium gene regulation through the cell cycle. 细胞周期中平衡基因调控的不合理有效性。

Cell systems Pub Date : 2024-07-17 Epub Date: 2024-07-08 DOI: 10.1016/j.cels.2024.06.002

Jose M G Vilar, Leonor Saiz

引用次数: 0