Pub Date : 2025-02-06DOI: 10.1016/j.isci.2025.111965
Thi Kim Cuong Phu , Phi Long Nguyen , Thi Viet Bac Phung
Electrocoagulation (EC) has been a well-known technology for wastewater treatment over the past centuries, owing to its straightforward equipment requirements and highly effective contaminant removal efficiency. This literature review emphasizes the influence of several input variables in the EC system such as electrode materials, applied current, pH, supporting electrolyte, and inner-electrode distance on effluent removal efficiency and energy consumption. Besides that, depending on the intrinsic properties of effluents, EC is recommended to hybridize with other methods such as physical-, biological-, chemical-, and electrochemical methods in order to enhance removal performance and reduce energy consumption. Subsequently, a comprehensive analysis of EC performance is presented, including power consumption, and evaluation of the synergistic effect of multiple input variables using statistical methods. Finally, this review discusses future perspectives such as the environmentally friendly utilization of post-EC treated sludges, the development of renewable energy-driven EC systems, and the challenges of EC management by artificial intelligence.
{"title":"Recent progress in highly effective electrocoagulation-coupled systems for advanced wastewater treatment","authors":"Thi Kim Cuong Phu , Phi Long Nguyen , Thi Viet Bac Phung","doi":"10.1016/j.isci.2025.111965","DOIUrl":"10.1016/j.isci.2025.111965","url":null,"abstract":"<div><div>Electrocoagulation (EC) has been a well-known technology for wastewater treatment over the past centuries, owing to its straightforward equipment requirements and highly effective contaminant removal efficiency. This literature review emphasizes the influence of several input variables in the EC system such as electrode materials, applied current, pH, supporting electrolyte, and inner-electrode distance on effluent removal efficiency and energy consumption. Besides that, depending on the intrinsic properties of effluents, EC is recommended to hybridize with other methods such as physical-, biological-, chemical-, and electrochemical methods in order to enhance removal performance and reduce energy consumption. Subsequently, a comprehensive analysis of EC performance is presented, including power consumption, and evaluation of the synergistic effect of multiple input variables using statistical methods. Finally, this review discusses future perspectives such as the environmentally friendly utilization of post-EC treated sludges, the development of renewable energy-driven EC systems, and the challenges of EC management by artificial intelligence.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111965"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem cell accumulation and mutation-derived tumors are two hallmarks of Drosophila midgut aging. They imply a decline in stem cell signaling homeostasis late in life and a robust homeostasis in young adults. Contrary to this, we find spontaneously developing stem-like cells that vary in size and ploidy, have a stem-enteroblast mixed identity, achieve higher mitotic rate per cell, exhibit DNA replication stress, and are inherently prone to clustering. Reduction of mitosis or DNA replication stress lessens the production of these cells but does not explain the loss of their proper differentiation. However, young enterocyte progenitors also display epigenetic plasticity in Notch signaling network genes and Notch locus instability. Strikingly, reinforcing Notch signaling in enteroblasts, alleviates dysplasia and extends overall survival and survival to infection. Thus, Notch signaling between prospective stem cells and enteroblasts is never sufficiently on, producing stem-enteroblast mixed identity cells that cluster and compromise homeostasis and overall aging.
{"title":"Aberrant enterocyte progenitor clustering as an early life biomarker of Drosophila aging","authors":"Constantina Neophytou , Savvas Teloni , Maria Koumouri , Marine Stefanutti , Panagiota Gianni , Vural Yilmaz , Katerina Strati , Yiorgos Apidianakis","doi":"10.1016/j.isci.2025.111967","DOIUrl":"10.1016/j.isci.2025.111967","url":null,"abstract":"<div><div>Stem cell accumulation and mutation-derived tumors are two hallmarks of <em>Drosophila</em> midgut aging. They imply a decline in stem cell signaling homeostasis late in life and a robust homeostasis in young adults. Contrary to this, we find spontaneously developing stem-like cells that vary in size and ploidy, have a stem-enteroblast mixed identity, achieve higher mitotic rate per cell, exhibit DNA replication stress, and are inherently prone to clustering. Reduction of mitosis or DNA replication stress lessens the production of these cells but does not explain the loss of their proper differentiation. However, young enterocyte progenitors also display epigenetic plasticity in Notch signaling network genes and <em>Notch</em> locus instability. Strikingly, reinforcing Notch signaling in enteroblasts, alleviates dysplasia and extends overall survival and survival to infection. Thus, Notch signaling between prospective stem cells and enteroblasts is never sufficiently on, producing stem-enteroblast mixed identity cells that cluster and compromise homeostasis and overall aging.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111967"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06eCollection Date: 2025-02-21DOI: 10.1016/j.isci.2025.111951
Qi Su, Sun Y Kim, Funmi Adewale, Ye Zhou, Christina Aldler, Min Ni, Yi Wei, Michael E Burczynski, Gurinder S Atwal, Mark W Sleeman, Andrew J Murphy, Yurong Xin, Xiping Cheng
[This corrects the article DOI: 10.1016/j.isci.2021.103233.].
{"title":"Erratum: Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver.","authors":"Qi Su, Sun Y Kim, Funmi Adewale, Ye Zhou, Christina Aldler, Min Ni, Yi Wei, Michael E Burczynski, Gurinder S Atwal, Mark W Sleeman, Andrew J Murphy, Yurong Xin, Xiping Cheng","doi":"10.1016/j.isci.2025.111951","DOIUrl":"https://doi.org/10.1016/j.isci.2025.111951","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.isci.2021.103233.].</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 2","pages":"111951"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.isci.2025.111920
Heming Zhang , S. Peter Goedegebuure , Li Ding , David DeNardo , Ryan C. Fields , Michael Province , Yixin Chen , Philip Payne , Fuhai Li
Multi-omic data-driven studies are at the forefront of precision medicine by characterizing complex disease signaling systems across multiple views and levels. The integration and interpretation of multi-omic data are critical for identifying disease targets and deciphering disease signaling pathways. However, it remains an open problem due to the complex signaling interactions among many proteins. Herein, we propose a multi-scale multi-hop multi-omic network flow model, M3NetFlow, to facilitate both hypothesis-guided and generic multi-omic data analysis tasks. We evaluated M3NetFlow using two independent case studies: (1) uncovering mechanisms of synergy of drug combinations (hypothesis/anchor-target guided multi-omic analysis) and (2) identifying biomarkers of Alzheimer’s disease (generic multi-omic analysis). The evaluation and comparison results showed that M3NetFlow achieved the best prediction accuracy and identified a set of drug combination synergy- and disease-associated targets. The model can be directly applied to other multi-omic data-driven studies.
{"title":"M3NetFlow: A multi-scale multi-hop graph AI model for integrative multi-omic data analysis","authors":"Heming Zhang , S. Peter Goedegebuure , Li Ding , David DeNardo , Ryan C. Fields , Michael Province , Yixin Chen , Philip Payne , Fuhai Li","doi":"10.1016/j.isci.2025.111920","DOIUrl":"10.1016/j.isci.2025.111920","url":null,"abstract":"<div><div>Multi-omic data-driven studies are at the forefront of precision medicine by characterizing complex disease signaling systems across multiple views and levels. The integration and interpretation of multi-omic data are critical for identifying disease targets and deciphering disease signaling pathways. However, it remains an open problem due to the complex signaling interactions among many proteins. Herein, we propose a multi-scale multi-hop multi-omic network flow model, M3NetFlow, to facilitate both hypothesis-guided and generic multi-omic data analysis tasks. We evaluated M3NetFlow using two independent case studies: (1) uncovering mechanisms of synergy of drug combinations (hypothesis/anchor-target guided multi-omic analysis) and (2) identifying biomarkers of Alzheimer’s disease (generic multi-omic analysis). The evaluation and comparison results showed that M3NetFlow achieved the best prediction accuracy and identified a set of drug combination synergy- and disease-associated targets. The model can be directly applied to other multi-omic data-driven studies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111920"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.isci.2025.111972
Shicheng Zhu , Suman Huo , Weiran He , Caiyan Huang , Jiannan Zhang , Xiaoning Jiang , Yeqing Qian , Chengyan Chen , Zhong-Min Dai , Xueqin Yang , Mengsheng Qiu , Tangliang Li , Xiao-Jing Zhu
The specific roles of nonsense-mediated mRNA decay (NMD), a translation-dependent RNA quality control mechanism that degrades mRNAs containing premature termination codons (PTCs), in mammalian craniofacial development have remained unclear. Here, we show that knockout of the essential NMD factor Smg5 in mouse craniofacial neural crest cells leads to hypoplastic mandibles, subsequently inducing tongue mispositioning and cleft palate formation. Furthermore, Smg5 loss triggers massive cell apoptosis and disrupts cell differentiation, accompanied by widespread alterations in alternative splicing and a surge in PTC-containing mRNA levels. Notably, the abnormal upregulation of a PTC-containing Porcn transcript leads to reduced Porcn protein and impaired Wnt5a/JNK signaling, a crucial pathway for craniofacial morphogenesis. Finally, death of Smg5-deficient craniofacial neural crest cells can be ameliorated by Wnt5a in craniofacial neural crest (CNC) in vitro explants. Taken together, our findings demonstrate that Smg5-mediated NMD regulates mammalian craniofacial development by fine-tuning Wnt signaling through post-transcriptional regulation of Porcn.
{"title":"Fine-tuning of Wnt signaling by RNA surveillance factor Smg5 in the mouse craniofacial development","authors":"Shicheng Zhu , Suman Huo , Weiran He , Caiyan Huang , Jiannan Zhang , Xiaoning Jiang , Yeqing Qian , Chengyan Chen , Zhong-Min Dai , Xueqin Yang , Mengsheng Qiu , Tangliang Li , Xiao-Jing Zhu","doi":"10.1016/j.isci.2025.111972","DOIUrl":"10.1016/j.isci.2025.111972","url":null,"abstract":"<div><div>The specific roles of nonsense-mediated mRNA decay (NMD), a translation-dependent RNA quality control mechanism that degrades mRNAs containing premature termination codons (PTCs), in mammalian craniofacial development have remained unclear. Here, we show that knockout of the essential NMD factor <em>Smg5</em> in mouse craniofacial neural crest cells leads to hypoplastic mandibles, subsequently inducing tongue mispositioning and cleft palate formation. Furthermore, <em>Smg5</em> loss triggers massive cell apoptosis and disrupts cell differentiation, accompanied by widespread alterations in alternative splicing and a surge in PTC-containing mRNA levels. Notably, the abnormal upregulation of a PTC-containing <em>Porcn</em> transcript leads to reduced Porcn protein and impaired Wnt5a/JNK signaling, a crucial pathway for craniofacial morphogenesis. Finally, death of Smg5<em>-</em>deficient craniofacial neural crest cells can be ameliorated by Wnt5a in craniofacial neural crest (CNC) <em>in vitro</em> explants. Taken together, our findings demonstrate that <em>Smg5</em>-mediated NMD regulates mammalian craniofacial development by fine-tuning Wnt signaling through post-transcriptional regulation of <em>Porcn</em>.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111972"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.isci.2025.111963
Jing Tang , Rui Shan , Peng Wang , Wei-Qiang Chen , Dungang Gu , Guanghui Li , Pinhua Rao , Jinguo Wang , Jiaqi Lu
Recent climate-trade policies emphasize managing carbon embedded in goods, with electricity carbon footprints as a key metric. However, the rapid energy transition complicates this evaluation. An innovative spatiotemporal model, accounting for dynamically-installed low-carbon energy infrastructure (LCPI), was developed to assess electricity decarbonization trajectories. Applying to Chinese power grid, the national and provincial electricity carbon footprints are projected to analyze the impact of LCPI deployment. By 2050, under aggressive decarbonization scenarios, the electricity carbon footprint is projected to reach 0.12 kg CO2-eq/kWh—a 38.13% reduction compared to scenarios that ignore LCPI decarbonization, and a 19.18% difference when neglecting the heterogeneous carbon footprint of spatiotemporally accumulated LCPI. Meanwhile, up to 57.94% of China’s electricity carbon footprint stems from historical LCPI production emissions, thereby stressing the long-lasting impact of renewable investments. Such insights support targeted policies to systematically reduce energy-related carbon footprints, providing a scalable roadmap for global sustainable energy practices.
{"title":"Deciphering decarbonization trajectories in China by spatiotemporal-accumulation modeling of electricity carbon footprint","authors":"Jing Tang , Rui Shan , Peng Wang , Wei-Qiang Chen , Dungang Gu , Guanghui Li , Pinhua Rao , Jinguo Wang , Jiaqi Lu","doi":"10.1016/j.isci.2025.111963","DOIUrl":"10.1016/j.isci.2025.111963","url":null,"abstract":"<div><div>Recent climate-trade policies emphasize managing carbon embedded in goods, with electricity carbon footprints as a key metric. However, the rapid energy transition complicates this evaluation. An innovative spatiotemporal model, accounting for dynamically-installed low-carbon energy infrastructure (LCPI), was developed to assess electricity decarbonization trajectories. Applying to Chinese power grid, the national and provincial electricity carbon footprints are projected to analyze the impact of LCPI deployment. By 2050, under aggressive decarbonization scenarios, the electricity carbon footprint is projected to reach 0.12 kg CO<sub>2</sub>-eq/kWh—a 38.13% reduction compared to scenarios that ignore LCPI decarbonization, and a 19.18% difference when neglecting the heterogeneous carbon footprint of spatiotemporally accumulated LCPI. Meanwhile, up to 57.94% of China’s electricity carbon footprint stems from historical LCPI production emissions, thereby stressing the long-lasting impact of renewable investments. Such insights support targeted policies to systematically reduce energy-related carbon footprints, providing a scalable roadmap for global sustainable energy practices.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111963"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05DOI: 10.1016/j.isci.2025.111961
Matthew Herring , Eva Särndahl , Oleksandr Kotlyar , Nikolai Scherbak , Magnus Engwall , Roger Karlsson , Mikael Ejdebäck , Alexander Persson , Andi Alijagic
Existing research has proven difficult to understand the interplay between upstream signaling events during NLRP3 inflammasome activation. Additionally, events downstream of inflammasome complex formation such as cytokine release and pyroptosis can exhibit variation, further complicating matters. Cell Painting has emerged as a prominent tool for unbiased evaluation of the effect of perturbations on cell morphological phenotypes. Using this technique, phenotypic fingerprints can be generated that reveal connections between phenotypes and possible modes of action. To the best of our knowledge, this was the first study that utilized Cell Painting on human THP-1 macrophages to generate phenotypic fingerprints in response to different endogenous and exogenous NLRP3 inflammasome triggers and to identify phenotypic features specific to NLRP3 inflammasome complex formation. Our results demonstrated that not only can Cell Painting generate morphological fingerprints that are NLRP3 trigger-specific but it can also identify cellular fingerprints associated with NLRP3 inflammasome activation.
{"title":"Exploring NLRP3-related phenotypic fingerprints in human macrophages using Cell Painting assay","authors":"Matthew Herring , Eva Särndahl , Oleksandr Kotlyar , Nikolai Scherbak , Magnus Engwall , Roger Karlsson , Mikael Ejdebäck , Alexander Persson , Andi Alijagic","doi":"10.1016/j.isci.2025.111961","DOIUrl":"10.1016/j.isci.2025.111961","url":null,"abstract":"<div><div>Existing research has proven difficult to understand the interplay between upstream signaling events during NLRP3 inflammasome activation. Additionally, events downstream of inflammasome complex formation such as cytokine release and pyroptosis can exhibit variation, further complicating matters. Cell Painting has emerged as a prominent tool for unbiased evaluation of the effect of perturbations on cell morphological phenotypes. Using this technique, phenotypic fingerprints can be generated that reveal connections between phenotypes and possible modes of action. To the best of our knowledge, this was the first study that utilized Cell Painting on human THP-1 macrophages to generate phenotypic fingerprints in response to different endogenous and exogenous NLRP3 inflammasome triggers and to identify phenotypic features specific to NLRP3 inflammasome complex formation. Our results demonstrated that not only can Cell Painting generate morphological fingerprints that are NLRP3 trigger-specific but it can also identify cellular fingerprints associated with NLRP3 inflammasome activation.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111961"},"PeriodicalIF":4.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143430066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05DOI: 10.1016/j.isci.2025.111886
Sunghee Lee , Jamie Gudyka , Marnie Skinner , Jasmin Ceja-Vega , Amani Rabadi , Christopher Poust , Caroline Scott , Micaela Panella , Elizabeth Andersen , Jessica Said
In the spirit of collaborative science, Prof. Sunghee Lee (Chemistry Professor at Iona University in New York, USA) embarked on her academic career with a vision to bring an interdisciplinary approach to undergraduate education. At a Predominantly Undergraduate Institution (PUI) such as Iona, she saw a unique opportunity to weave together teaching and research, creating a rich tapestry of learning experiences for students.
Her goal was simple yet ambitious: to use research as a bridge connecting classroom theory to real-world interdisciplinary scientific practice.
In this Backstory, Sunghee and her students and recent graduates reflect on the development and experiences that shaped their journey through Project Symphony and the resulting skills they’ve learned. The symphony they’ve created together is a testament to the transformative power of collaborative undergraduate research – a melody of discovery that continues to evolve and inspire.
{"title":"Project symphony: Composing a masterpiece in a science laboratory","authors":"Sunghee Lee , Jamie Gudyka , Marnie Skinner , Jasmin Ceja-Vega , Amani Rabadi , Christopher Poust , Caroline Scott , Micaela Panella , Elizabeth Andersen , Jessica Said","doi":"10.1016/j.isci.2025.111886","DOIUrl":"10.1016/j.isci.2025.111886","url":null,"abstract":"<div><div>In the spirit of collaborative science, Prof. Sunghee Lee (Chemistry Professor at Iona University in New York, USA) embarked on her academic career with a vision to bring an interdisciplinary approach to undergraduate education. At a Predominantly Undergraduate Institution (PUI) such as Iona, she saw a unique opportunity to weave together teaching and research, creating a rich tapestry of learning experiences for students.</div><div>Her goal was simple yet ambitious: to use research as a bridge connecting classroom theory to real-world interdisciplinary scientific practice.</div><div>In this Backstory, Sunghee and her students and recent graduates reflect on the development and experiences that shaped their journey through <em>Project Symphony</em> and the resulting skills they’ve learned. The symphony they’ve created together is a testament to the transformative power of collaborative undergraduate research – a melody of discovery that continues to evolve and inspire.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 2","pages":"Article 111886"},"PeriodicalIF":4.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143267937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05DOI: 10.1016/j.isci.2025.111956
Michala G. Rolver , Juan Camacho-Roda , Yifan Dai , Mette Flinck , Renata Ialchina , Julie Hindkær , Rigmor T. Dyhr , August N. Bodilsen , Nanditha S. Prasad , Jonathan Baldan , Jiayi Yao , Albin Sandelin , Luis Arnes , Stine F. Pedersen
The acidic tumor microenvironment (TME) favors cancer aggressiveness via incompletely understood pathways. Here, we asked whether adaptation to environmental acidosis (pH 6.5) selects for human pancreatic cancer stem cell (CSC) properties. RNA sequencing (RNA-seq) of acid-adapted (AA) Panc-1 cells revealed CSC pathway enrichment and upregulation of CSC markers. AA Panc-1 cells exhibited classical CSC characteristics including increased aldehyde dehydrogenase (ALDH) activity and β-catenin activity. Panc-1, PaTu8988s, and MiaPaCa-2 cells all exhibited increased pancreatosphere-forming efficiency after acid adaptation but differed in CSC marker expression and did not exhibit typical flow cytometric CSC populations. However, single-nucleus sequencing revealed the acid adaptation-induced emergence of Panc-1 cell subpopulations with clear CSC characteristics. In orthotopic mouse tumors, AA Panc-1 cells exhibited enhanced aggressiveness, liver and lung metastasis, compared to controls. Collectively, our work suggests that acid adaptation enriches for pancreatic CSC phenotypes with unusual traits via several trajectories, providing new insight into how acidic microenvironments favor cancer aggressiveness.
{"title":"Tumor microenvironment acidosis favors pancreatic cancer stem cell properties and in vivo metastasis","authors":"Michala G. Rolver , Juan Camacho-Roda , Yifan Dai , Mette Flinck , Renata Ialchina , Julie Hindkær , Rigmor T. Dyhr , August N. Bodilsen , Nanditha S. Prasad , Jonathan Baldan , Jiayi Yao , Albin Sandelin , Luis Arnes , Stine F. Pedersen","doi":"10.1016/j.isci.2025.111956","DOIUrl":"10.1016/j.isci.2025.111956","url":null,"abstract":"<div><div>The acidic tumor microenvironment (TME) favors cancer aggressiveness via incompletely understood pathways. Here, we asked whether adaptation to environmental acidosis (pH 6.5) selects for human pancreatic cancer stem cell (CSC) properties. RNA sequencing (RNA-seq) of acid-adapted (AA) Panc-1 cells revealed CSC pathway enrichment and upregulation of CSC markers. AA Panc-1 cells exhibited classical CSC characteristics including increased aldehyde dehydrogenase (ALDH) activity and β-catenin activity. Panc-1, PaTu8988s, and MiaPaCa-2 cells all exhibited increased pancreatosphere-forming efficiency after acid adaptation but differed in CSC marker expression and did not exhibit typical flow cytometric CSC populations. However, single-nucleus sequencing revealed the acid adaptation-induced emergence of Panc-1 cell subpopulations with clear CSC characteristics. In orthotopic mouse tumors, AA Panc-1 cells exhibited enhanced aggressiveness, liver and lung metastasis, compared to controls. Collectively, our work suggests that acid adaptation enriches for pancreatic CSC phenotypes with unusual traits via several trajectories, providing new insight into how acidic microenvironments favor cancer aggressiveness.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111956"},"PeriodicalIF":4.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05DOI: 10.1016/j.isci.2025.111959
Alexander George , Naghmeh Akhavan , Bradford E. Peercy , Michelle Starz-Gaiano
Migratory cells respond to graded concentrations of diffusible chemoattractants in vitro, but how complex tissue geometries in vivo impact chemotaxis is poorly understood. To address this, we studied the Drosophila border cells. Live-imaged border cells varied in their chemotactic migration speeds, which correlated positionally with distinct architectures. We then developed a reduced mathematical model to determine how chemoattractant distribution is affected by tissue architecture. Larger extracellular volumes locally dampened the chemoattractant gradient and, when coupled with an agent-based motion of the cluster, reduced cell speeds. This suggests that chemoattractant levels vary by tissue architectures, informing cell migration behaviors locally, which we tested in vivo. Genetically elevating chemoattractant levels slowed migration in specific architectural regions, while mutants with spacious tissue structure rescued defects from high chemoattractant levels, promoting punctual migration. Our results highlight the interplay between tissue geometry and the local distribution of signaling molecules to orchestrate cell migration.
{"title":"Chemotaxis of Drosophila border cells is modulated by tissue geometry through dispersion of chemoattractants","authors":"Alexander George , Naghmeh Akhavan , Bradford E. Peercy , Michelle Starz-Gaiano","doi":"10.1016/j.isci.2025.111959","DOIUrl":"10.1016/j.isci.2025.111959","url":null,"abstract":"<div><div>Migratory cells respond to graded concentrations of diffusible chemoattractants <em>in vitro</em>, but how complex tissue geometries <em>in vivo</em> impact chemotaxis is poorly understood. To address this, we studied the Drosophila border cells. Live-imaged border cells varied in their chemotactic migration speeds, which correlated positionally with distinct architectures. We then developed a reduced mathematical model to determine how chemoattractant distribution is affected by tissue architecture. Larger extracellular volumes locally dampened the chemoattractant gradient and, when coupled with an agent-based motion of the cluster, reduced cell speeds. This suggests that chemoattractant levels vary by tissue architectures, informing cell migration behaviors locally, which we tested <em>in vivo.</em> Genetically elevating chemoattractant levels slowed migration in specific architectural regions, while mutants with spacious tissue structure rescued defects from high chemoattractant levels, promoting punctual migration. Our results highlight the interplay between tissue geometry and the local distribution of signaling molecules to orchestrate cell migration.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111959"},"PeriodicalIF":4.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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