Cell systems最新文献

Tracking the gene expression programs and clonal relationships that underlie mast, myeloid, and T lineage specification from stem cells.

Cell systems Pub Date : 2024-12-18 Epub Date: 2024-11-29 DOI: 10.1016/j.cels.2024.11.001

Yale S Michaels, Matthew C Major, Becca Bonham-Carter, Jingqi Zhang, Tiam Heydari, John M Edgar, Mona M Siu, Laura Greenstreet, Roser Vilarrasa-Blasi, Seungjoon Kim, Elizabeth L Castle, Aden Forrow, M Iliana Ibanez-Rios, Carla Zimmerman, Yvonne Chung, Tara Stach, Nico Werschler, David J H F Knapp, Roser Vento-Tormo, Geoffrey Schiebinger, Peter W Zandstra

{"title":"Tracking the gene expression programs and clonal relationships that underlie mast, myeloid, and T lineage specification from stem cells.","authors":"Yale S Michaels, Matthew C Major, Becca Bonham-Carter, Jingqi Zhang, Tiam Heydari, John M Edgar, Mona M Siu, Laura Greenstreet, Roser Vilarrasa-Blasi, Seungjoon Kim, Elizabeth L Castle, Aden Forrow, M Iliana Ibanez-Rios, Carla Zimmerman, Yvonne Chung, Tara Stach, Nico Werschler, David J H F Knapp, Roser Vento-Tormo, Geoffrey Schiebinger, Peter W Zandstra","doi":"10.1016/j.cels.2024.11.001","DOIUrl":"10.1016/j.cels.2024.11.001","url":null,"abstract":"T cells develop from hematopoietic progenitors in the thymus and protect against pathogens and cancer. However, the emergence of human T cell-competent blood progenitors and their subsequent specification to the T lineage have been challenging to capture in real time. Here, we leveraged a pluripotent stem cell differentiation system to understand the transcriptional dynamics and cell fate restriction events that underlie this critical developmental process. Time-resolved single-cell RNA sequencing revealed that downregulation of the multipotent hematopoietic program, upregulation of >90 lineage-associated transcription factors, and cell-cycle exit all occur within a highly coordinated developmental window. Gene-regulatory network inference uncovered a role for YBX1 in T lineage specification. We mapped the differentiation cell fate hierarchy using transcribed lineage barcoding and discovered that mast and myeloid potential bifurcate from each other early in hematopoiesis, upstream of T lineage restriction. Our systems-level analyses provide a quantitative, time-resolved model of human T cell fate specification. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1245-1263.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775404","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

Optimized reporters for multiplexed detection of transcription factor activity.

Cell systems Pub Date : 2024-12-18 Epub Date: 2024-12-06 DOI: 10.1016/j.cels.2024.11.003

Max Trauernicht, Teodora Filipovska, Chaitanya Rastogi, Bas van Steensel

引用次数: 0

Tailoring microbial fitness through computational steering and CRISPRi-driven robustness regulation. 通过计算引导和 CRISPRi- 驱动的稳健性调控来定制微生物的适应性。

Cell systems Pub Date : 2024-12-18 Epub Date: 2024-12-11 DOI: 10.1016/j.cels.2024.11.012

Bin Yang, Chao Wu, Yuxi Teng, Katherine J Chou, Michael T Guarnieri, Wei Xiong

{"title":"Tailoring microbial fitness through computational steering and CRISPRi-driven robustness regulation.","authors":"Bin Yang, Chao Wu, Yuxi Teng, Katherine J Chou, Michael T Guarnieri, Wei Xiong","doi":"10.1016/j.cels.2024.11.012","DOIUrl":"10.1016/j.cels.2024.11.012","url":null,"abstract":"The widespread application of genetically modified microorganisms (GMMs) across diverse sectors underscores the pressing need for robust strategies to mitigate the risks associated with their potential uncontrolled escape. This study merges computational modeling with CRISPR interference (CRISPRi) to refine GMM metabolic robustness. Utilizing ensemble modeling, we achieved high-throughput in silico screening for enzymatic targets susceptible to expression alterations. Translating these insights, we developed functional CRISPRi, boosting fitness control via multiplexed gene knockdown. Our method, enhanced by an insulator-improved gRNA structure and an off-switch circuit controlling a compact Cas12m, resulted in rationally engineered strains with escape frequencies below National Institutes of Health standards. The effectiveness of this approach was confirmed under various conditions, showcasing its ability for secure GMM management. This research underscores the resilience of microbial metabolism, strategically modifying key nodes to halt growth without provoking significant resistance, thereby enabling more reliable and precise GMM control. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1133-1147.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819613","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

Cracking the code of adaptive immunity: The role of computational tools.

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.009

Kasi Vegesana, Paul G Thomas

引用次数: 0

Reading the repertoire: Progress in adaptive immune receptor analysis using machine learning.

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.006

Timothy J O'Donnell, Chakravarthi Kanduri, Giulio Isacchini, Julien P Limenitakis, Rebecca A Brachman, Raymond A Alvarez, Ingrid H Haff, Geir K Sandve, Victor Greiff

引用次数: 0

Unveiling the hidden network of STING's subcellular regulation.

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.014

Xiaoqi Sun, Brian D Brown

引用次数: 0

Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques. 多模态数据的马尔可夫场网络模型可预测免疫系统扰动对猕猴静脉注射卡介苗的影响。

Cell systems Pub Date : 2024-12-18 Epub Date: 2024-11-05 DOI: 10.1016/j.cels.2024.10.001

Shu Wang, Amy J Myers, Edward B Irvine, Chuangqi Wang, Pauline Maiello, Mark A Rodgers, Jaime Tomko, Kara Kracinovsky, H Jacob Borish, Michael C Chao, Douaa Mugahid, Patricia A Darrah, Robert A Seder, Mario Roederer, Charles A Scanga, Philana Ling Lin, Galit Alter, Sarah M Fortune, JoAnne L Flynn, Douglas A Lauffenburger

{"title":"Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques.","authors":"Shu Wang, Amy J Myers, Edward B Irvine, Chuangqi Wang, Pauline Maiello, Mark A Rodgers, Jaime Tomko, Kara Kracinovsky, H Jacob Borish, Michael C Chao, Douaa Mugahid, Patricia A Darrah, Robert A Seder, Mario Roederer, Charles A Scanga, Philana Ling Lin, Galit Alter, Sarah M Fortune, JoAnne L Flynn, Douglas A Lauffenburger","doi":"10.1016/j.cels.2024.10.001","DOIUrl":"10.1016/j.cels.2024.10.001","url":null,"abstract":"Analysis of multi-modal datasets can identify multi-scale interactions underlying biological systems but can be beset by spurious connections due to indirect impacts propagating through an unmapped biological network. For example, studies in macaques have shown that Bacillus Calmette-Guerin (BCG) vaccination by an intravenous route protects against tuberculosis, correlating with changes across various immune data modes. To eliminate spurious correlations and identify critical immune interactions in a public multi-modal dataset (systems serology, cytokines, and cytometry) of vaccinated macaques, we applied Markov fields (MFs), a data-driven approach that explains vaccine efficacy and immune correlations via multivariate network paths, without requiring large numbers of samples (i.e., macaques) relative to multivariate features. We find that integrating multiple data modes with MFs helps remove spurious connections. Finally, we used the MF to predict outcomes of perturbations at various immune nodes, including an experimentally validated B cell depletion that induced network-wide shifts without reducing vaccine protection.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1278-1294.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592417","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

Evaluating predictive patterns of antigen-specific B cells by single-cell transcriptome and antibody repertoire sequencing.

Cell systems Pub Date : 2024-12-18 Epub Date: 2024-12-10 DOI: 10.1016/j.cels.2024.11.005

Lena Erlach, Raphael Kuhn, Andreas Agrafiotis, Danielle Shlesinger, Alexander Yermanos, Sai T Reddy

{"title":"Evaluating predictive patterns of antigen-specific B cells by single-cell transcriptome and antibody repertoire sequencing.","authors":"Lena Erlach, Raphael Kuhn, Andreas Agrafiotis, Danielle Shlesinger, Alexander Yermanos, Sai T Reddy","doi":"10.1016/j.cels.2024.11.005","DOIUrl":"10.1016/j.cels.2024.11.005","url":null,"abstract":"The field of antibody discovery typically involves extensive experimental screening of B cells from immunized animals. Machine learning (ML)-guided prediction of antigen-specific B cells could accelerate this process but requires sufficient training data with antigen-specificity labeling. Here, we introduce a dataset of single-cell transcriptome and antibody repertoire sequencing of B cells from immunized mice, which are labeled as antigen specific or non-specific through experimental selections. We identify gene expression patterns associated with antigen specificity by differential gene expression analysis and assess their antibody sequence diversity. Subsequently, we benchmark various ML models, both linear and non-linear, trained on different combinations of gene expression and antibody repertoire features. Additionally, we assess transfer learning using features from general and antibody-specific protein language models (PLMs). Our findings show that gene expression-based models outperform sequence-based models for antigen-specificity predictions, highlighting a promising avenue for computationally guided antibody discovery.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1295-1303.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815269","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

A three-node Turing gene circuit forms periodic spatial patterns in bacteria.

Cell systems Pub Date : 2024-12-18 Epub Date: 2024-12-02 DOI: 10.1016/j.cels.2024.11.002

Jure Tica, Martina Oliver Huidobro, Tong Zhu, Georg K A Wachter, Roozbeh H Pazuki, Dario G Bazzoli, Natalie S Scholes, Elisa Tonello, Heike Siebert, Michael P H Stumpf, Robert G Endres, Mark Isalan

{"title":"A three-node Turing gene circuit forms periodic spatial patterns in bacteria.","authors":"Jure Tica, Martina Oliver Huidobro, Tong Zhu, Georg K A Wachter, Roozbeh H Pazuki, Dario G Bazzoli, Natalie S Scholes, Elisa Tonello, Heike Siebert, Michael P H Stumpf, Robert G Endres, Mark Isalan","doi":"10.1016/j.cels.2024.11.002","DOIUrl":"10.1016/j.cels.2024.11.002","url":null,"abstract":"Turing patterns are self-organizing systems that can form spots, stripes, or labyrinths. Proposed examples in tissue organization include zebrafish pigmentation, digit spacing, and many others. The theory of Turing patterns in biology has been debated because of their stringent fine-tuning requirements, where patterns only occur within a small subset of parameters. This has complicated the engineering of synthetic Turing gene circuits from first principles, although natural genetic Turing networks have been identified. Here, we engineered a synthetic genetic reaction-diffusion system where three nodes interact according to a non-classical Turing network with improved parametric robustness. The system reproducibly generated stationary, periodic, concentric stripe patterns in growing E. coli colonies. A partial differential equation model reproduced the patterns, with a Turing parameter regime obtained by fitting to experimental data. Our synthetic Turing system can contribute to nanotechnologies, such as patterned biomaterial deposition, and provide insights into developmental patterning programs. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1123-1132.e3"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775397","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

Microengineered in vitro CAR T cell screens and assays.

Cell systems Pub Date : 2024-12-18 DOI: 10.1016/j.cels.2024.11.011

Jaehoon Kim, Susan Napier Thomas

引用次数: 0