Cell systems最新文献_第5页

The molecular landscape of cellular metal ion biology. 细胞金属离子生物学的分子景观。

Cell systems Pub Date : 2025-07-16 Epub Date: 2025-06-13 DOI: 10.1016/j.cels.2025.101319

Simran Kaur Aulakh, Oliver Lemke, Lukasz Szyrwiel, Stephan Kamrad, Yu Chen, Johannes Hartl, Michael Mülleder, Jens Nielsen, Markus Ralser

引用次数: 0

Resolving the design principles that control post-natal vascular growth and scaling. 解决控制产后血管生长和缩放的设计原则。

IF 7.7

Cell systems Pub Date : 2025-07-16 Epub Date: 2025-07-07 DOI: 10.1016/j.cels.2025.101324

Danielle Pi, Jonas Braun, Sayantan Dutta, Debabrata Patra, Pauline Bougaran, Ana Mompeón, Feiyang Ma, Stuart R Stock, Sharon Choi, Lourdes García-Ortega, Muhammad Yogi Pratama, Diomarys Pichardo, Bhama Ramkhelawon, Rui Benedito, Victoria L Bautch, David M Ornitz, Yogesh Goyal, M Luisa Iruela-Arispe

{"title":"Resolving the design principles that control post-natal vascular growth and scaling.","authors":"Danielle Pi, Jonas Braun, Sayantan Dutta, Debabrata Patra, Pauline Bougaran, Ana Mompeón, Feiyang Ma, Stuart R Stock, Sharon Choi, Lourdes García-Ortega, Muhammad Yogi Pratama, Diomarys Pichardo, Bhama Ramkhelawon, Rui Benedito, Victoria L Bautch, David M Ornitz, Yogesh Goyal, M Luisa Iruela-Arispe","doi":"10.1016/j.cels.2025.101324","DOIUrl":"10.1016/j.cels.2025.101324","url":null,"abstract":"After birth, tissues grow until they reach adult size, with each organ exhibiting unique cellular dynamics, growth patterns, and stem or non-stem cell sources. Using multiscale experimental and computational approaches, we found that aortic enlargement follows distinct growth principles, scaling with the vertebral column. Expansion proceeds via two temporally coordinated, spatially stochastic waves of proliferation aligned with blood flow, each with unique cell-cycle kinetics, with the first wave featuring cycles as short as 6 h. Single-cell RNA sequencing revealed increased fatty acid metabolism accompanying cell enlargement. Mathematical modeling and experiments showed that endothelial cell extrusion is essential for maintaining homeostatic aortic size as it adjusts for proliferation excess. Using a genetic model of achondroplasia, we mechanistically demonstrated that the aorta preserves proper scaling by increasing cell extrusion while keeping proliferation rates intact. These findings provide a blueprint of the principles orchestrating aortic growth, which relies entirely on the proliferation of resident differentiated cells. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101324"},"PeriodicalIF":7.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593180","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

The metallome and the biological periodic table: A metal atlas in cells. 金属组和生物元素周期表：细胞中的金属图谱。

Cell systems Pub Date : 2025-07-16 DOI: 10.1016/j.cels.2025.101344

Hongyan Li, Hongzhe Sun

引用次数: 0

SPaSE: Spatially resolved pathology scores using optimal transport on spatial transcriptomics data. SPaSE：在空间转录组学数据上使用最佳转运的空间解决病理评分。

IF 7.7

Cell systems Pub Date : 2025-07-16 Epub Date: 2025-06-05 DOI: 10.1016/j.cels.2025.101301

Mohammad Nuwaisir Rahman, Mohammed Abid Abrar, Vikram Rakesh Shaw, James F Martin, M Saifur Rahman, Md Abul Hassan Samee

{"title":"SPaSE: Spatially resolved pathology scores using optimal transport on spatial transcriptomics data.","authors":"Mohammad Nuwaisir Rahman, Mohammed Abid Abrar, Vikram Rakesh Shaw, James F Martin, M Saifur Rahman, Md Abul Hassan Samee","doi":"10.1016/j.cels.2025.101301","DOIUrl":"10.1016/j.cels.2025.101301","url":null,"abstract":"Pathological events often impact tissue regions in a spatially variable manner, making it challenging to identify therapeutic targets. Spatial transcriptomics (ST) is a powerful technology to map spatially variable molecular mechanisms, yet suitable analytical methods have been lacking. We introduce spatially resolved pathology score (SPaSE), an optimal transport-based algorithm to compare ST data from diseased and control tissues. SPaSE computes a \"pathology score\" for each spot in the diseased sample, quantifying the pathological impact at that spot. In post-myocardial infarction (post-MI) mouse hearts, these scores delineated zones that matched independent expert annotations. Modeling pathology scores from gene expression revealed signatures predictive of varying pathological severity. The scoring model learned from mouse data showed accurate predictions on human post-MI data. We also demonstrated SPaSE's efficacy on additional simulated and real ST data from traumatic brain injury and Duchenne muscular dystrophy mouse models. SPaSE is a useful addition to the existing ST algorithms. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101301"},"PeriodicalIF":7.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251316","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

Systematic analysis of the effects of splicing on the diversity of post-translational modifications in protein isoforms using PTM-POSE. 利用PTM-POSE系统分析剪接对蛋白质同工型翻译后修饰多样性的影响。

Cell systems Pub Date : 2025-07-16 Epub Date: 2025-06-12 DOI: 10.1016/j.cels.2025.101318

Sam Crowl, Maeve Bella Coleman, Andrew Chaphiv, Ben T Jordan, Kristen M Naegle

{"title":"Systematic analysis of the effects of splicing on the diversity of post-translational modifications in protein isoforms using PTM-POSE.","authors":"Sam Crowl, Maeve Bella Coleman, Andrew Chaphiv, Ben T Jordan, Kristen M Naegle","doi":"10.1016/j.cels.2025.101318","DOIUrl":"10.1016/j.cels.2025.101318","url":null,"abstract":"Post-translational modifications (PTMs) and splicing are both important regulatory processes controlling protein function; therefore, we developed PTM-POSE (PTM projection onto splice events) to explore the interplay between them. PTM-POSE identifies potential PTM sites associated with alternative isoforms or splice events, enabling comprehensive analysis of how PTMs affect isoform function, protein interactions, and enzymatic regulation. Through systematic analysis of Ensembl transcripts with PTM-POSE, we highlighted two key mechanisms by which splicing diversifies PTMs across isoforms-exclusion of a PTM site (32%) or alteration of the flanking sequences surrounding the PTM (2%). In experiment-specific analysis of PTM-associated splicing events, we identified the potential rewiring of protein-interaction and kinase-substrate networks, suggesting coordinated connections between PTM signaling. We provide our tool and associated data publicly to enable further exploration of splicing-PTM relationships. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101318"},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295509","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

Machine-guided dual-objective protein engineering for deimmunization and therapeutic functions. 机器引导的双目标蛋白工程用于脱免疫和治疗功能。

IF 7.7

Cell systems Pub Date : 2025-07-16 Epub Date: 2025-06-03 DOI: 10.1016/j.cels.2025.101299

Eric Wolfsberg, Jean-Sebastien Paul, Josh Tycko, Binbin Chen, Michael C Bassik, Lacramioara Bintu, Ash A Alizadeh, Xiaojing J Gao

{"title":"Machine-guided dual-objective protein engineering for deimmunization and therapeutic functions.","authors":"Eric Wolfsberg, Jean-Sebastien Paul, Josh Tycko, Binbin Chen, Michael C Bassik, Lacramioara Bintu, Ash A Alizadeh, Xiaojing J Gao","doi":"10.1016/j.cels.2025.101299","DOIUrl":"10.1016/j.cels.2025.101299","url":null,"abstract":"Cell and gene therapies often express nonhuman proteins, which carry a risk of anti-therapy immunogenicity. An emerging consensus is to instead use modified human protein domains, but these domains include nonhuman peptides around mutated residues and at interdomain junctions, which may also be immunogenic. We present a modular workflow to optimize protein function and minimize immunogenicity by using existing machine learning models that predict protein function and peptide-major histocompatibility complex (MHC) presentation. We first applied this workflow to existing transcriptional activation and RNA-binding domains by removing potentially immunogenic MHC II epitopes. We then generated small-molecule-controllable transcription factors with human-derived DNA-binding domains targeting non-genomic DNA sequences. Finally, we established a workflow for creating deimmunized zinc-finger arrays to target arbitrary DNA sequences and upregulated two therapeutically relevant genes, utrophin (UTRN) and sodium voltage-gated channel alpha subunit 1 (SCN1A), using it. Our modular workflow offers a way to potentially make cell and gene therapies safer and more efficacious using state-of-the-art algorithms.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101299"},"PeriodicalIF":7.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227978","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

Impossible ecologies: Interaction networks and stability of coexistence in ecological communities. 不可能的生态：生态群落中共存的相互作用网络与稳定性。

Cell systems Pub Date : 2025-07-16 Epub Date: 2025-06-17 DOI: 10.1016/j.cels.2025.101297

Yu Meng, Szabolcs Horvát, Carl D Modes, Pierre A Haas

{"title":"Impossible ecologies: Interaction networks and stability of coexistence in ecological communities.","authors":"Yu Meng, Szabolcs Horvát, Carl D Modes, Pierre A Haas","doi":"10.1016/j.cels.2025.101297","DOIUrl":"10.1016/j.cels.2025.101297","url":null,"abstract":"Does an ecological community allow stable species coexistence? Identifying the general effects of competitive, mutualistic, and predator-prey interactions on stability remains a central problem of systems ecology because established approaches cannot account for the full network arrangement of these interactions. Here, we therefore analyze all interaction networks of N≤5 species with Lotka-Volterra dynamics by combining exact results and numerical exploration. We find that a very small subset of these networks is \"impossible ecologies,\" in which stable coexistence is non-trivially impossible. We prove that the possibility of stable coexistence is determined by similarly rare \"irreducible ecologies.\" Statistical sampling shows that this probability varies over orders of magnitude even in ecologies that differ only in the network arrangement of identical interactions. Thus, our approach reveals that the full network structure of interactions can influence stability of coexistence more than the established effect of interaction-type proportions. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101297"},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318949","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

Designing quantitative gene therapy on ComMAND. 按指令设计定量基因治疗。

Cell systems Pub Date : 2025-06-18 DOI: 10.1016/j.cels.2025.101323

Connie An, Noa Katz, Xiaojing J Gao

引用次数: 0

A systems view of cellular heterogeneity: Unlocking the "wheel of fate". 细胞异质性的系统观点：解开“命运之轮”。

Cell systems Pub Date : 2025-06-18 Epub Date: 2025-06-04 DOI: 10.1016/j.cels.2025.101300

Hourieh Movasat, Enzo Giacopino, Ali Shahdoost, Yeganeh Dorri Nokoorani, Ali Houshyar Abrbekouh, Yaser Tahamtani, Nika Shakiba

{"title":"A systems view of cellular heterogeneity: Unlocking the \"wheel of fate\".","authors":"Hourieh Movasat, Enzo Giacopino, Ali Shahdoost, Yeganeh Dorri Nokoorani, Ali Houshyar Abrbekouh, Yaser Tahamtani, Nika Shakiba","doi":"10.1016/j.cels.2025.101300","DOIUrl":"10.1016/j.cels.2025.101300","url":null,"abstract":"Systems biology offers a view of the cell as an input-output device: a biochemical network (or cellular \"processor\") that interprets cues from the microenvironment to drive cell fate. Advancements in single-cell technologies are unlocking the cellular black box, revealing heterogeneity in seemingly homogeneous cell populations. But are these differences technical variability or biology? In this review, we explore this question through a systems biology lens, offering a framework for conceptualizing heterogeneity from the cell's perspective and summarizing systems and synthetic biology tools for capturing heterogeneity. While cellular inputs shape the probability of attaining particular fates, each cell spins a stochastic \"wheel of fate.\" Applying this framework, we explore heterogeneity in two case studies: human pluripotent stem cell (hPSC) culture and beta cell differentiation. Looking forward, we discuss how a systems approach to heterogeneity may enable more predictable outcomes in stem cell research, with broad implications for developmental biology and regenerative medicine.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101300"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236142","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

Uncovering the principles coordinating systems-level organelle biogenesis with cellular growth. 揭示系统级细胞器生物发生与细胞生长的协调原理。

Cell systems Pub Date : 2025-06-18 Epub Date: 2025-06-06 DOI: 10.1016/j.cels.2025.101267

Shixing Wang, Deepthi Kailash, Shankar Mukherji

{"title":"Uncovering the principles coordinating systems-level organelle biogenesis with cellular growth.","authors":"Shixing Wang, Deepthi Kailash, Shankar Mukherji","doi":"10.1016/j.cels.2025.101267","DOIUrl":"10.1016/j.cels.2025.101267","url":null,"abstract":"A complete framework of eukaryotic cellular growth control must include the growth of its defining hallmarks: organelles. Organelle coordination with cellular growth is opaque without measuring multiple organelles in the same cell with adequate statistics to test theoretical frameworks. Here, we map out the correlation structure of systems-level organelle biogenesis with cellular growth using \"rainbow yeast,\" simultaneously visualizing 6 major metabolically active organelles. Hyperspectral imaging of thousands of rainbow yeast cells revealed that systems-level organelle biogenesis is organized into collective organelle modes activated by changes in nutrient availability. Chemical biological dissection suggests that sensed growth rate and cell size specifically activate these organelle modes. Mathematical modeling and synthetic control of cytoplasmic availability suggest that the organelle mode structure allows growth homeostasis in constant environments and responsiveness to environmental change. This regulatory architecture may underlie how compartmentalization allows cell size and growth rate flexibility to satisfy otherwise incompatible environmental and developmental constraints.","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101267"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251317","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