Cell systems最新文献_第9页

Self-resistance-gene-guided, high-throughput automated genome mining of bioactive natural products from Streptomyces. 链霉菌生物活性天然产物的自抗性基因引导、高通量自动基因组挖掘。

Cell systems Pub Date : 2025-03-19 Epub Date: 2025-03-11 DOI: 10.1016/j.cels.2025.101237

Yujie Yuan, Chunshuai Huang, Nilmani Singh, Guanhua Xun, Huimin Zhao

{"title":"Self-resistance-gene-guided, high-throughput automated genome mining of bioactive natural products from Streptomyces.","authors":"Yujie Yuan, Chunshuai Huang, Nilmani Singh, Guanhua Xun, Huimin Zhao","doi":"10.1016/j.cels.2025.101237","DOIUrl":"10.1016/j.cels.2025.101237","url":null,"abstract":"Natural products (NPs) from bacteria, fungi, and plants are a vital source of drug leads, with Streptomyces species being particularly significant due to their capability of producing diverse bioactive compounds. Here, we present a fully automated, scalable, high-throughput platform for discovering bioactive NPs in Streptomyces (FAST-NPS). This platform integrates computational biosynthetic gene cluster (BGC) prediction and prioritization guided by self-resistance genes, automated cloning and heterologous expression, high-throughput fermentation, and product extraction. As a proof of concept, we cloned 105 BGCs (10-100 kb) from 11 Streptomyces strains with a 95% success rate. Heterologous expression in Streptomyces lividans TK24 led to the detection of 23 NPs, including 8 with antibacterial or antitumor bioactivities from 5 BGCs. This work highlights the potential of FAST-NPS to accelerate bioactive NP discovery for biomedical and biotechnological applications. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101237"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617374","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

Engineering highly active nuclease enzymes with machine learning and high-throughput screening. 利用机器学习和高通量筛选技术设计高活性核酸酶。

Cell systems Pub Date : 2025-03-19 Epub Date: 2025-03-12 DOI: 10.1016/j.cels.2025.101236

Neil Thomas, David Belanger, Chenling Xu, Hanson Lee, Kathleen Hirano, Kosuke Iwai, Vanja Polic, Kendra D Nyberg, Kevin G Hoff, Lucas Frenz, Charlie A Emrich, Jun W Kim, Mariya Chavarha, Abi Ramanan, Jeremy J Agresti, Lucy J Colwell

{"title":"Engineering highly active nuclease enzymes with machine learning and high-throughput screening.","authors":"Neil Thomas, David Belanger, Chenling Xu, Hanson Lee, Kathleen Hirano, Kosuke Iwai, Vanja Polic, Kendra D Nyberg, Kevin G Hoff, Lucas Frenz, Charlie A Emrich, Jun W Kim, Mariya Chavarha, Abi Ramanan, Jeremy J Agresti, Lucy J Colwell","doi":"10.1016/j.cels.2025.101236","DOIUrl":"10.1016/j.cels.2025.101236","url":null,"abstract":"Optimizing enzymes to function in novel chemical environments is a central goal of synthetic biology, but optimization is often hindered by a rugged fitness landscape and costly experiments. In this work, we present TeleProt, a machine learning (ML) framework that blends evolutionary and experimental data to design diverse protein libraries, and employ it to improve the catalytic activity of a nuclease enzyme that degrades biofilms that accumulate on chronic wounds. After multiple rounds of high-throughput experiments, TeleProt found a significantly better top-performing enzyme than directed evolution (DE), had a better hit rate at finding diverse, high-activity variants, and was even able to design a high-performance initial library using no prior experimental data. We have released a dataset of 55,000 nuclease variants, one of the most extensive genotype-phenotype enzyme activity landscapes to date, to drive further progress in ML-guided design. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101236"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626689","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

Tissue sculpting with light. 组织雕刻与光。

Cell systems Pub Date : 2025-03-19 DOI: 10.1016/j.cels.2025.101241

Romane Petit, Léo Valon

引用次数: 0

Multiplexed dynamic control of temperature to probe and observe mammalian cells. 对温度进行多重动态控制，以探测和观察哺乳动物细胞。

Cell systems Pub Date : 2025-03-19 Epub Date: 2025-03-12 DOI: 10.1016/j.cels.2025.101234

William Benman, Pavan Iyengar, Thomas R Mumford, Zikang Huang, Manya Kapoor, Grace Liu, Lukasz J Bugaj

引用次数: 0

Large-scale control over collective cell migration using light-activated epidermal growth factor receptors. 利用光激活表皮生长因子受体对集体细胞迁移的大规模控制。

IF 7.7

Cell systems Pub Date : 2025-03-19 Epub Date: 2025-03-03 DOI: 10.1016/j.cels.2025.101203

Kevin Suh, Richard H Thornton, Long Nguyen, Payam E Farahani, Daniel J Cohen, Jared E Toettcher

{"title":"Large-scale control over collective cell migration using light-activated epidermal growth factor receptors.","authors":"Kevin Suh, Richard H Thornton, Long Nguyen, Payam E Farahani, Daniel J Cohen, Jared E Toettcher","doi":"10.1016/j.cels.2025.101203","DOIUrl":"10.1016/j.cels.2025.101203","url":null,"abstract":"Receptor tyrosine kinases (RTKs) play key roles in coordinating cell movement at both single-cell and tissue scales. The recent development of optogenetic tools for controlling RTKs and their downstream signaling pathways suggests that these responses may be amenable to engineering-based control for sculpting tissue shape and function. Here, we report that a light-controlled epidermal growth factor (EGF) receptor (OptoEGFR) can be deployed in epithelial cells for precise, programmable control of long-range tissue movements. We show that in OptoEGFR-expressing tissues, light can drive millimeter-scale cell rearrangements to densify interior regions or produce rapid outgrowth at tissue edges. Light-controlled tissue movements are driven primarily by phosphoinositide 3-kinase (PI3K) signaling, rather than diffusible ligands, tissue contractility, or ERK kinase signaling as seen in other RTK-driven migration contexts. Our study suggests that synthetic, light-controlled RTKs could serve as a powerful platform for controlling cell positions and densities for diverse applications, including wound healing and tissue morphogenesis.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101203"},"PeriodicalIF":7.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560400","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

SPARROW reveals microenvironment-zone-specific cell states in healthy and diseased tissues. SPARROW揭示了健康和病变组织中微环境区特异性细胞状态。

Cell systems Pub Date : 2025-03-19 DOI: 10.1016/j.cels.2025.101235

Peiyao A Zhao, Ruoxin Li, Temi Adewunmi, Jessica Garber, Claire Gustafson, June Kim, Jocelin Malone, Adam Savage, Peter Skene, Xiao-Jun Li

{"title":"SPARROW reveals microenvironment-zone-specific cell states in healthy and diseased tissues.","authors":"Peiyao A Zhao, Ruoxin Li, Temi Adewunmi, Jessica Garber, Claire Gustafson, June Kim, Jocelin Malone, Adam Savage, Peter Skene, Xiao-Jun Li","doi":"10.1016/j.cels.2025.101235","DOIUrl":"10.1016/j.cels.2025.101235","url":null,"abstract":"Spatially resolved transcriptomics technologies have advanced our understanding of cellular characteristics within tissue contexts. However, current analytical tools often treat cell-type inference and cellular neighborhood identification as separate and hard clustering processes, limiting comparability across scales and samples. SPARROW addresses these challenges by jointly learning latent embeddings and soft clusterings of cell types and cellular organization. It outperformed state-of-the-art methods in cell-type inference and microenvironment zone delineation and uncovered zone-specific cell states in human and mouse tissues that competing methods missed. By integrating spatially resolved transcriptomics and single-cell RNA sequencing (scRNA-seq) data in a shared latent space, SPARROW achieves single-cell spatial resolution and whole-transcriptome coverage, enabling the discovery of both established and unknown microenvironment zone-specific ligand-receptor interactions in the human tonsil. Overall, SPARROW is a computational framework that provides a comprehensive characterization of tissue features across scales, samples, and conditions.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"16 3","pages":"101235"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672011","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

Cold and hot fibrosis define clinically distinct cardiac pathologies. 冷纤维化和热纤维化定义了临床上不同的心脏病理。

Cell systems Pub Date : 2025-03-19 Epub Date: 2025-02-18 DOI: 10.1016/j.cels.2025.101198

Shoval Miyara, Miri Adler, Kfir B Umansky, Daniel Häußler, Elad Bassat, Yalin Divinsky, Jacob Elkahal, David Kain, Daria Lendengolts, Ricardo O Ramirez Flores, Hanna Bueno-Levy, Ofra Golani, Tali Shalit, Michael Gershovits, Eviatar Weizman, Alexander Genzelinakh, Danielle M Kimchi, Avraham Shakked, Lingling Zhang, Jingkui Wang, Andrea Baehr, Zachary Petrover, Rachel Sarig, Tatjana Dorn, Alessandra Moretti, Julio Saez-Rodriguez, Christian Kupatt, Elly M Tanaka, Ruslan Medzhitov, Achim Krüger, Avi Mayo, Uri Alon, Eldad Tzahor

{"title":"Cold and hot fibrosis define clinically distinct cardiac pathologies.","authors":"Shoval Miyara, Miri Adler, Kfir B Umansky, Daniel Häußler, Elad Bassat, Yalin Divinsky, Jacob Elkahal, David Kain, Daria Lendengolts, Ricardo O Ramirez Flores, Hanna Bueno-Levy, Ofra Golani, Tali Shalit, Michael Gershovits, Eviatar Weizman, Alexander Genzelinakh, Danielle M Kimchi, Avraham Shakked, Lingling Zhang, Jingkui Wang, Andrea Baehr, Zachary Petrover, Rachel Sarig, Tatjana Dorn, Alessandra Moretti, Julio Saez-Rodriguez, Christian Kupatt, Elly M Tanaka, Ruslan Medzhitov, Achim Krüger, Avi Mayo, Uri Alon, Eldad Tzahor","doi":"10.1016/j.cels.2025.101198","DOIUrl":"10.1016/j.cels.2025.101198","url":null,"abstract":"Fibrosis remains a major unmet medical need. Simplifying principles are needed to better understand fibrosis and to yield new therapeutic approaches. Fibrosis is driven by myofibroblasts that interact with macrophages. A mathematical cell-circuit model predicts two types of fibrosis: hot fibrosis driven by macrophages and myofibroblasts and cold fibrosis driven by myofibroblasts alone. Testing these concepts in cardiac fibrosis resulting from myocardial infarction (MI) and heart failure (HF), we revealed that acute MI leads to cold fibrosis whereas chronic injury (HF) leads to hot fibrosis. MI-driven cold fibrosis is conserved in pigs and humans. We computationally identified a vulnerability of cold fibrosis: the myofibroblast autocrine growth factor loop. Inhibiting this loop by targeting TIMP1 with neutralizing antibodies reduced myofibroblast proliferation and fibrosis post-MI in mice. Our study demonstrates the utility of the concepts of hot and cold fibrosis and the feasibility of a circuit-to-target approach to pinpoint a treatment strategy that reduces fibrosis. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101198"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461028","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

How well do contextual protein encodings learn structure, function, and evolutionary context? 背景蛋白编码如何学习结构、功能和进化背景？

Cell systems Pub Date : 2025-03-19 Epub Date: 2025-03-04 DOI: 10.1016/j.cels.2025.101201

Sai Pooja Mahajan, Fátima A Dávila-Hernández, Jeffrey A Ruffolo, Jeffrey J Gray

{"title":"How well do contextual protein encodings learn structure, function, and evolutionary context?","authors":"Sai Pooja Mahajan, Fátima A Dávila-Hernández, Jeffrey A Ruffolo, Jeffrey J Gray","doi":"10.1016/j.cels.2025.101201","DOIUrl":"10.1016/j.cels.2025.101201","url":null,"abstract":"In proteins, the optimal residue at any position is determined by its structural, evolutionary, and functional contexts-much like how a word may be inferred from its context in language. We trained masked label prediction models to learn representations of amino acid residues in different contexts. We focus questions on evolution and structural flexibility and whether and how contextual encodings derived through pretraining and fine-tuning may improve representations for specialized contexts. Sequences sampled from our learned representations fold into template structure and reflect sequence variations seen in related proteins. For flexible proteins, sampled sequences traverse the full conformational space of the native sequence, suggesting that plasticity is encoded in the template structure. For protein-protein interfaces, generated sequences replicate wild-type binding energies across diverse interfaces and binding strengths in silico. For the antibody-antigen interface, fine-tuning recapitulate conserved sequence patterns, while pretraining on general contexts improves sequence recovery for the hypervariable H3 loop. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101201"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12026297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569193","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

DeST-OT: Alignment of spatiotemporal transcriptomics data. est - ot：时空转录组学数据比对。

Cell systems Pub Date : 2025-02-19 Epub Date: 2025-01-27 DOI: 10.1016/j.cels.2024.12.001

Peter Halmos, Xinhao Liu, Julian Gold, Feng Chen, Li Ding, Benjamin J Raphael

引用次数: 0

Should biology put complexity first? 生物学应该把复杂性放在第一位吗？

Cell systems Pub Date : 2025-02-19 Epub Date: 2025-02-10 DOI: 10.1016/j.cels.2025.101197

Philip Ball

引用次数: 0