Cell systemsPub Date : 2025-02-19Epub Date: 2025-02-10DOI: 10.1016/j.cels.2025.101197
Philip Ball
{"title":"Should biology put complexity first?","authors":"Philip Ball","doi":"10.1016/j.cels.2025.101197","DOIUrl":"10.1016/j.cels.2025.101197","url":null,"abstract":"<p><p>The dictum \"Everything should be made as simple as possible, but no simpler\" poses a problem for biology. How simply can it be told without doing damage to its complex nature? The answer might be found by relinquishing tidy but misleading stories that begin with genes and molecules and recognizing that even complex systems have generic principles.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101197"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400705","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}
Cell systemsPub Date : 2025-02-19Epub Date: 2025-01-27DOI: 10.1016/j.cels.2024.12.001
Peter Halmos, Xinhao Liu, Julian Gold, Feng Chen, Li Ding, Benjamin J Raphael
{"title":"DeST-OT: Alignment of spatiotemporal transcriptomics data.","authors":"Peter Halmos, Xinhao Liu, Julian Gold, Feng Chen, Li Ding, Benjamin J Raphael","doi":"10.1016/j.cels.2024.12.001","DOIUrl":"10.1016/j.cels.2024.12.001","url":null,"abstract":"<p><p>Spatially resolved transcriptomics (SRT) measures mRNA transcripts at thousands of locations within a tissue slice, revealing spatial variations in gene expression and cell types. SRT has been applied to tissue slices from multiple time points during the development of an organism. We introduce developmental spatiotemporal optimal transport (DeST-OT), a method to align spatiotemporal transcriptomics data using optimal transport (OT). DeST-OT uses semi-relaxed OT to model cellular growth, death, and differentiation processes. We also derive a growth distortion metric and a migration metric to quantify the plausibility of spatiotemporal alignments. DeST-OT outperforms existing methods on the alignment of spatiotemporal transcriptomics data from developing mouse kidney and axolotl brain. DeST-OT estimated growth rates also provide insights into the gene expression programs governing the growth and differentiation of cells over space and time.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101160"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061657","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}
Cell systemsPub Date : 2025-02-19DOI: 10.1016/j.cels.2025.101199
Y Erin Chen
{"title":"A genetic toolbox for engineering C. acnes.","authors":"Y Erin Chen","doi":"10.1016/j.cels.2025.101199","DOIUrl":"https://doi.org/10.1016/j.cels.2025.101199","url":null,"abstract":"<p><p>Cutibacterium acnes is a highly prevalent and abundant skin bacterium that lives deep in the hair follicle, a unique site for host access. Thus, it is a prime target to engineer. This study introduces a genetic toolbox for C. acnes, which will enable basic science and therapeutic bioengineering.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"16 2","pages":"101199"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470303","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}
Cell systemsPub Date : 2025-02-19Epub Date: 2025-02-03DOI: 10.1016/j.cels.2025.101195
Shang Li, Qunlun Shen, Shihua Zhang
{"title":"Spatial transcriptomics-aided localization for single-cell transcriptomics with STALocator.","authors":"Shang Li, Qunlun Shen, Shihua Zhang","doi":"10.1016/j.cels.2025.101195","DOIUrl":"10.1016/j.cels.2025.101195","url":null,"abstract":"<p><p>Single-cell RNA-sequencing (scRNA-seq) techniques can measure gene expression at single-cell resolution but lack spatial information. Spatial transcriptomics (ST) techniques simultaneously provide gene expression data and spatial information. However, the data quality of the spatial resolution or gene coverage is still much lower than the quality of the single-cell transcriptomics data. To this end, we develop a ST-Aided Locator for single-cell transcriptomics (STALocator) to localize single cells to corresponding ST data. Applications on simulated data showed that STALocator performed better than other localization methods. When applied to the human brain and squamous cell carcinoma data, STALocator could robustly reconstruct the relative spatial organization of critical cell populations. Moreover, STALocator could enhance gene expression patterns for Slide-seqV2 data and predict genome-wide gene expression data for fluorescence in situ hybridization (FISH) and Xenium data, leading to the identification of more spatially variable genes and more biologically relevant Gene Ontology (GO) terms compared with the raw data. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101195"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191539","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}
Cell systemsPub Date : 2025-02-19Epub Date: 2025-02-11DOI: 10.1016/j.cels.2025.101171
Andrew G Wang, Minjun Son, Aleksandr Gorin, Emma Kenna, Abinash Padhi, Bijentimala Keisham, Adam Schauer, Alexander Hoffmann, Savaş Tay
{"title":"Macrophage memory emerges from coordinated transcription factor and chromatin dynamics.","authors":"Andrew G Wang, Minjun Son, Aleksandr Gorin, Emma Kenna, Abinash Padhi, Bijentimala Keisham, Adam Schauer, Alexander Hoffmann, Savaş Tay","doi":"10.1016/j.cels.2025.101171","DOIUrl":"10.1016/j.cels.2025.101171","url":null,"abstract":"<p><p>Cells of the immune system operate in dynamic microenvironments where the timing, concentration, and order of signaling molecules constantly change. Despite this complexity, immune cells manage to communicate accurately and control inflammation and infection. It is unclear how these dynamic signals are encoded and decoded and if individual cells retain the memory of past exposure to inflammatory molecules. Here, we use live-cell analysis, ATAC sequencing, and an in vivo model of sepsis to show that sequential inflammatory signals induce memory in individual macrophages through reprogramming the nuclear factor κB (NF-κB) network and the chromatin accessibility landscape. We use transcriptomic profiling and deep learning to show that transcription factor and chromatin dynamics coordinate fine-tuned macrophage responses to new inflammatory signals. This work demonstrates how macrophages retain the memory of previous signals despite single-cell variability and elucidates the mechanisms of signal-induced memory in dynamic inflammatory conditions like sepsis.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101171"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412008","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}
Cell systemsPub Date : 2025-02-19Epub Date: 2025-01-17DOI: 10.1016/j.cels.2024.12.008
Benjamin A Doran, Robert Y Chen, Hannah Giba, Vivek Behera, Bidisha Barat, Anitha Sundararajan, Huaiying Lin, Ashley Sidebottom, Eric G Pamer, Arjun S Raman
{"title":"Subspecies phylogeny in the human gut revealed by co-evolutionary constraints across the bacterial kingdom.","authors":"Benjamin A Doran, Robert Y Chen, Hannah Giba, Vivek Behera, Bidisha Barat, Anitha Sundararajan, Huaiying Lin, Ashley Sidebottom, Eric G Pamer, Arjun S Raman","doi":"10.1016/j.cels.2024.12.008","DOIUrl":"10.1016/j.cels.2024.12.008","url":null,"abstract":"<p><p>The human gut microbiome contains many bacterial strains of the same species (\"strain-level variants\") that shape microbiome function. The tremendous scale and molecular resolution at which microbial communities are being interrogated motivates addressing how to describe strain-level variants. We introduce the \"Spectral Tree\"-an inferred tree of relatedness built from patterns of co-evolutionary constraint between greater than 7,000 diverse bacteria. Using the Spectral Tree to describe over 600 diverse gut commensal strains that we isolated, whole-genome sequenced, and metabolically profiled revealed (1) widespread phylogenetic structure among strain-level variants, (2) the origins of subspecies phylogeny as a shared history of phage infections across humans, and (3) the key role of inter-human strain variation in predicting strain-level metabolic qualities. Overall, our work demonstrates the existence and metabolic importance of structured phylogeny below the level of species for commensal gut bacteria, motivating a redefinition of individual strains according to their evolutionary context. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101167"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018343","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}
Cell systemsPub Date : 2025-02-19Epub Date: 2025-02-12DOI: 10.1016/j.cels.2025.101196
Almut Heinken, Timothy Otto Hulshof, Bram Nap, Filippo Martinelli, Arianna Basile, Amy O'Brolchain, Neil Francis O'Sullivan, Celine Gallagher, Eimer Magee, Francesca McDonagh, Ian Lalor, Maeve Bergin, Phoebe Evans, Rachel Daly, Ronan Farrell, Rose Mary Delaney, Saoirse Hill, Saoirse Roisin McAuliffe, Trevor Kilgannon, Ronan M T Fleming, Cyrille C Thinnes, Ines Thiele
{"title":"A genome-scale metabolic reconstruction resource of 247,092 diverse human microbes spanning multiple continents, age groups, and body sites.","authors":"Almut Heinken, Timothy Otto Hulshof, Bram Nap, Filippo Martinelli, Arianna Basile, Amy O'Brolchain, Neil Francis O'Sullivan, Celine Gallagher, Eimer Magee, Francesca McDonagh, Ian Lalor, Maeve Bergin, Phoebe Evans, Rachel Daly, Ronan Farrell, Rose Mary Delaney, Saoirse Hill, Saoirse Roisin McAuliffe, Trevor Kilgannon, Ronan M T Fleming, Cyrille C Thinnes, Ines Thiele","doi":"10.1016/j.cels.2025.101196","DOIUrl":"10.1016/j.cels.2025.101196","url":null,"abstract":"<p><p>Genome-scale modeling of microbiome metabolism enables the simulation of diet-host-microbiome-disease interactions. However, current genome-scale reconstruction resources are limited in scope by computational challenges. We developed an optimized and highly parallelized reconstruction and analysis pipeline to build a resource of 247,092 microbial genome-scale metabolic reconstructions, deemed APOLLO. APOLLO spans 19 phyla, contains >60% of uncharacterized strains, and accounts for strains from 34 countries, all age groups, and multiple body sites. Using machine learning, we predicted with high accuracy the taxonomic assignment of strains based on the computed metabolic features. We then built 14,451 metagenomic sample-specific microbiome community models to systematically interrogate their community-level metabolic capabilities. We show that sample-specific metabolic pathways accurately stratify microbiomes by body site, age, and disease state. APOLLO is freely available, enables the systematic interrogation of the metabolic capabilities of largely still uncultured and unclassified species, and provides unprecedented opportunities for systems-level modeling of personalized host-microbiome co-metabolism.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101196"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416386","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}
Cell systemsPub Date : 2025-02-19Epub Date: 2025-02-07DOI: 10.1016/j.cels.2025.101168
Christoph Zechner, Frank Jülicher
{"title":"Concentration buffering and noise reduction in non-equilibrium phase-separating systems.","authors":"Christoph Zechner, Frank Jülicher","doi":"10.1016/j.cels.2025.101168","DOIUrl":"10.1016/j.cels.2025.101168","url":null,"abstract":"<p><p>Biomolecular condensates have been proposed to buffer intracellular concentrations and reduce noise. However, concentrations need not be buffered in multicomponent systems, leading to a non-constant saturation concentration (c<sub>sat</sub>) when individual components are varied. Simplified equilibrium considerations suggest that noise reduction might be closely related to concentration buffering and that a fixed saturation concentration is required for noise reduction to be effective. Here, we present a theoretical analysis to demonstrate that these suggestions do not apply to mesoscopic fluctuating systems. We show that concentration buffering and noise reduction are distinct concepts, which cannot be used interchangeably. We further demonstrate that concentration buffering and a constant c<sub>sat</sub> are neither necessary nor sufficient for noise reduction to be effective. Clarity about these concepts is important for studying the role of condensates in controlling cellular noise and for the interpretation of concentration relationships in cells. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101168"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375047","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}
{"title":"Inferring cell trajectories of spatial transcriptomics via optimal transport analysis.","authors":"Xunan Shen, Lulu Zuo, Zhongfei Ye, Zhongyang Yuan, Ke Huang, Zeyu Li, Qichao Yu, Xuanxuan Zou, Xiaoyu Wei, Ping Xu, Yaqi Deng, Xin Jin, Xun Xu, Liang Wu, Hongmei Zhu, Pengfei Qin","doi":"10.1016/j.cels.2025.101194","DOIUrl":"10.1016/j.cels.2025.101194","url":null,"abstract":"<p><p>The integration of cell transcriptomics and spatial position to organize differentiation trajectories remains a challenge. Here, we introduce SpaTrack, which leverages optimal transport to reconcile both gene expression and spatial position from spatial transcriptomics into the transition costs, thereby reconstructing cell differentiation. SpaTrack can construct detailed spatial trajectories that reflect the differentiation topology and trace cell dynamics across multiple samples over temporal intervals. To capture the dynamic drivers of differentiation, SpaTrack models cell fate as a function of expression profiles influenced by transcription factors over time. By applying SpaTrack, we successfully disentangle spatiotemporal trajectories of axolotl telencephalon regeneration and mouse midbrain development. Diverse malignant lineages expanding within a primary tumor are uncovered. One lineage, characterized by upregulated epithelial mesenchymal transition, implants at the metastatic site and subsequently colonizes to form a secondary tumor. Overall, SpaTrack efficiently advances trajectory inference from spatial transcriptomics, providing valuable insights into differentiation processes.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101194"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191538","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}
Cell systemsPub Date : 2025-02-19Epub Date: 2025-02-06DOI: 10.1016/j.cels.2025.101169
Guillermo Nevot, Javier Santos-Moreno, Nil Campamà-Sanz, Lorena Toloza, Cristóbal Parra-Cid, Patrick A M Jansen, Içvara Barbier, Rodrigo Ledesma-Amaro, Ellen H van den Bogaard, Marc Güell
{"title":"Synthetically programmed antioxidant delivery by a domesticated skin commensal.","authors":"Guillermo Nevot, Javier Santos-Moreno, Nil Campamà-Sanz, Lorena Toloza, Cristóbal Parra-Cid, Patrick A M Jansen, Içvara Barbier, Rodrigo Ledesma-Amaro, Ellen H van den Bogaard, Marc Güell","doi":"10.1016/j.cels.2025.101169","DOIUrl":"10.1016/j.cels.2025.101169","url":null,"abstract":"<p><p>Bacteria represent a promising dynamic delivery system for the treatment of disease. In the skin, the relevant location of Cutibacterium acnes within the hair follicle makes this bacterium an attractive chassis for dermal biotechnological applications. Here, we provide a genetic toolbox for the engineering of this traditionally intractable bacterium, including basic gene expression tools, biocontainment strategies, markerless genetic engineering, and dynamic transcriptional regulation. As a proof of concept, we develop an antioxidant-secreting strain capable of reducing oxidative stress in a UV stress model.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101169"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371408","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}
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