iMetaOmicsPub Date : 2026-07-17eCollection Date: 2026-09-01DOI: 10.1002/imo2.70123
Lei Li, Shuai Liu, Zhijun Cao, Yangchun Cao, Shengru Wu, Lu Deng, Junhu Yao, Jun Zhang
{"title":"Bile acid metabolism and signaling in human and animal health: A One Health perspective.","authors":"Lei Li, Shuai Liu, Zhijun Cao, Yangchun Cao, Shengru Wu, Lu Deng, Junhu Yao, Jun Zhang","doi":"10.1002/imo2.70123","DOIUrl":"10.1002/imo2.70123","url":null,"abstract":"<p><p>The One Health concept emphasizes the interdependence of human, animal, and ecosystem health. Against this broad backdrop, bile acids (BAs), as central products of host-microbiota co-metabolism, act far beyond their classical role in lipid emulsification. This review systematically summarizes BA biosynthesis, enterohepatic circulation, and gut microbiota-mediated metabolic modification. We highlight how gut microbiota-derived secondary BAs and farnesoid X receptor and Takeda G protein-coupled receptor 5-mediated BA signaling together shape BA homeostasis, glucose and lipid metabolism, intestinal barrier integrity, and immune homeostasis. We further discuss how population diversity, circadian rhythm, diet, behavior, environmental exposure, and surgical interventions dynamically shape systemic BA profiles. Finally, from a One Health perspective, we highlight the translational potential of BA-targeted strategies in hepatobiliary diseases, metabolic disorders, neurodegenerative and retinal degenerative diseases, and intestinal infections, as well as their value in animal production as non-antibiotic nutritional regulators. By improving animal health and reducing excessive drug use, residues, and risks of antimicrobial resistance at the source, BA-based precision nutrition may contribute to food safety and ecosystem health. Overall, this review positions BAs as key molecular hubs in One Health, linking host metabolism, gut microbiota, immune regulation, and the integrated health of humans, animals, and ecosystems.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70123"},"PeriodicalIF":0.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217788","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}
iMetaOmicsPub Date : 2026-07-17eCollection Date: 2026-09-01DOI: 10.1002/imo2.70121
Zeping Gui, Huidong Su, Yuhao Chen, Jixing Yuan, Yexiu Gao, Ze Yu, Jing Zhang, Qingyi Zhu, Min Gu, Mulong Du, Zijie Wang, Ming Chen
{"title":"Ragomics-Meta: An open-source, scalable, reproducible, and extensible multi-omics analysis workflow.","authors":"Zeping Gui, Huidong Su, Yuhao Chen, Jixing Yuan, Yexiu Gao, Ze Yu, Jing Zhang, Qingyi Zhu, Min Gu, Mulong Du, Zijie Wang, Ming Chen","doi":"10.1002/imo2.70121","DOIUrl":"10.1002/imo2.70121","url":null,"abstract":"<p><p>Ragomics-Meta is an open-source, scalable, and reproducible multi-omics workflow for metabolism-centered analysis (https://www.raganetwork.com/). It integrates scRNA/snRNA-seq, spatial transcriptomics, scATAC-seq, and metabolomics modules to support quality control, dimensionality reduction, clustering, differential expression and accessibility analyses, pathway activity scoring, cell-cell communication inference, transcription-factor network analysis, and spatial metabolism exploration. By incorporating established tools such as Scanpy, Seurat, Squidpy, COMMOT, SnapATAC2, MEBOCOST, scMetabolism, AUCell, and a curated gutMGene-based resource, Ragomics-Meta enables systematic characterization of tumor metabolic programs and host-microbiome interactions. AI-assisted interpretation further facilitates biological annotation and hypothesis generation, providing a user-friendly framework for integrative single-cell and spatial multi-omics analysis.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70121"},"PeriodicalIF":0.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218106","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}
iMetaOmicsPub Date : 2026-07-14eCollection Date: 2026-09-01DOI: 10.1002/imo2.70125
Abdelhafid Bendahmane
{"title":"A pan-genome framework for exploiting germplasm diversity and structural variation in rose breeding.","authors":"Abdelhafid Bendahmane","doi":"10.1002/imo2.70125","DOIUrl":"10.1002/imo2.70125","url":null,"abstract":"<p><p>The urgent need for diverse rose cultivars requires better use of germplasm resources. Zhang et al. generated a rose pan-genome from 26 accessions, revealing structural variation and introgression linked to flowering, double flowers, and petal color, providing a valuable resource for molecular rose breeding.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70125"},"PeriodicalIF":0.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218098","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}
iMetaOmicsPub Date : 2026-07-09eCollection Date: 2026-09-01DOI: 10.1002/imo2.70114
Aolong Zhou, Cheng Guo, Mahmoud M Abdelsattar, Ahmad R Musa, Mequanint Biks, Abdullahi A Musa, Shahnaz Rahman, Abera Teshome Aleli, Pei Zhong, Jiawei Zhang, Junwei Cui, Xiyan Kou, Qingyuan Yu, Caijuan Yue, Qin Li, Dan Zhang, Zixuan Peng, Ao Ren, Ziqi Tian, Ziqi Liu, Yaona Zhang, Lili Zhang, Dina Karmallah, Naifeng Zhang, Tao Ma, Yan Tu, Qiyu Diao, Guijie Zhang, Xiaofeng Xu, Yanliang Bi
{"title":"Harnessing microbial metabolism and nutrition to target the gut-mammary axis for better livestock production and health.","authors":"Aolong Zhou, Cheng Guo, Mahmoud M Abdelsattar, Ahmad R Musa, Mequanint Biks, Abdullahi A Musa, Shahnaz Rahman, Abera Teshome Aleli, Pei Zhong, Jiawei Zhang, Junwei Cui, Xiyan Kou, Qingyuan Yu, Caijuan Yue, Qin Li, Dan Zhang, Zixuan Peng, Ao Ren, Ziqi Tian, Ziqi Liu, Yaona Zhang, Lili Zhang, Dina Karmallah, Naifeng Zhang, Tao Ma, Yan Tu, Qiyu Diao, Guijie Zhang, Xiaofeng Xu, Yanliang Bi","doi":"10.1002/imo2.70114","DOIUrl":"10.1002/imo2.70114","url":null,"abstract":"<p><p>The gut-mammary axis orchestrates bidirectional crosstalk linking intestinal homeostasis and mammary function through integrated neural, endocrine, and immune pathways. Dysregulation driven by gut microbiota dysbiosis or metabolic dysfunction compromises lactation performance and induces mastitis via pathogen translocation and epigenetic reprogramming. This review systematically discusses the molecular mechanisms underlying microbial metabolite-mediated mammary development and lactation efficiency, evaluates the impact of gut-derived pathogens on mammary barrier integrity and inflammatory cascades, explores maternal offspring microbiome transmission for neonatal immunity programming, and proposes precise nutritional strategies targeting microbial immune metabolic networks. Our synthesis of previous research findings aimed to optimize animal productivity, prevent mammary gland disorders, and provide insights for the advancement of the livestock industry.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70114"},"PeriodicalIF":0.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217953","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}
{"title":"A synthetic community promotes macadamia growth via root-microbe interactions and systemic plant responses.","authors":"Xiaofang Yao, Qiumei Liu, Wenlin Wang, Qiujin Tan, Chunheng Zhou, Dejun Li","doi":"10.1002/imo2.70122","DOIUrl":"10.1002/imo2.70122","url":null,"abstract":"<p><p>We employed an 18-month pot experiment and an integrated multi-omics approach to elucidate the potential mechanisms underlying synthetic community (SynCom)-mediated macadamia growth promotion. SynCom inoculation enhanced soil nitrogen cycling and potential nutrient (<i>e.g</i>., iron) acquisition. It simultaneously increased soil extracellular enzyme activities and enriched beneficial bacteria such as <i>Rhodanobacter</i>, <i>Ferrovibrio</i>, and <i>Rhodoblastus</i> in the root compartment. In addition, SynCom inoculation promoted the accumulation of rhizosphere metabolites, including the microbial siderophore pyochelin, and drove the co-enrichment of transcriptomic and metabolomic pathways, notably the arginine biosynthesis pathway. This coordinated response may have stimulated nitrogen and iron cycling in the soil, thereby promoting the healthy growth of macadamia.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70122"},"PeriodicalIF":0.0,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218105","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}
iMetaOmicsPub Date : 2026-07-08eCollection Date: 2026-09-01DOI: 10.1002/imo2.70119
Zhen Shen, Xingchen Li, Zhijun Gong, Yang Hu, Yongjiu Cai, Keqiang Shao, Guang Gao, Robbie M Martin, Xiangming Tang
{"title":"Warm-wet transition restructures arid lake microbiomes and functional potential.","authors":"Zhen Shen, Xingchen Li, Zhijun Gong, Yang Hu, Yongjiu Cai, Keqiang Shao, Guang Gao, Robbie M Martin, Xiangming Tang","doi":"10.1002/imo2.70119","DOIUrl":"10.1002/imo2.70119","url":null,"abstract":"<p><p>Over the past six decades, northwestern China has undergone a pronounced climatic transition from a \"warm-dry\" to a \"warm-wet\" regime, driving substantial shifts in lake water level (WL), salinity, and nutrient conditions. However, how this hydroclimatic transition restructures lake microbiomes and their functional potential remains poorly understood. Here, we used Lake Bosten, the largest inland lake in arid northwestern China, as a model ecosystem to examine the long-term impacts of climate-driven environmental change on microbial diversity, community assembly, network structure, and functional potential. We combined (1) meteorological and aquatic environmental records from 1958 to 2022, (2) decade-separated field surveys of microbial communities (2010-2011 vs. 2021-2022) using amplicon sequencing and metagenomics, and (3) mesocosm experiments simulating projected future hydroclimatic conditions. Warm-wet conditions influenced the Lake Bosten ecosystem through two main pathways: direct temperature effects and indirect WL mediated effects on hydrological connectivity and water chemistry. Field observations showed that the warm-wet period was characterized by higher WL, lower salinity and total nitrogen, and increased bacterial and eukaryotic diversity. Community assembly shifted toward stronger homogeneous selection and weaker dispersal limitation in both bacterial and eukaryotic communities, consistent with enhanced hydrological connectivity. At the same time, both microbial domains showed reduced community stability, and their co-occurrence networks exhibited lower complexity and structural stability. In contrast, broad metagenomic functional composition showed no significant shift despite pronounced taxonomic and network reorganization. Nitrogen cycling genes showed pathway-specific redistribution, with enhanced nitrogen fixation and selected nitrification related genes but reduced nitrate reduction, denitrification, and dissimilatory nitrate reduction to ammonium (DNRA). Taxon-function linkage further indicated that functional compensation was mainly mediated by replacement within bacterial functional guilds. Overall, our study links warm-wet hydroclimatic change to altered water level, salinity, nutrient conditions, microbiome restructuring, cross domain network rewiring, and buffered functional potential in an arid lake.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70119"},"PeriodicalIF":0.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218081","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}
iMetaOmicsPub Date : 2026-07-04eCollection Date: 2026-09-01DOI: 10.1002/imo2.70118
José Coche-Miranda, Patricio Arros, Nicolás Canales, Camilo Berríos-Pastén, Gastón Azziz, Rosalba Lagos, Julieta Orlando, Francisco P Chávez, Andrés E Marcoleta
{"title":"Antarctic soil microbiomes encode structurally conserved and phylogenetically diverse beta-lactamases.","authors":"José Coche-Miranda, Patricio Arros, Nicolás Canales, Camilo Berríos-Pastén, Gastón Azziz, Rosalba Lagos, Julieta Orlando, Francisco P Chávez, Andrés E Marcoleta","doi":"10.1002/imo2.70118","DOIUrl":"10.1002/imo2.70118","url":null,"abstract":"<p><p>Antimicrobial resistance is a major global health threat shaped not only by clinical settings but also by environmental reservoirs, in line with the One Health framework. Antarctic and Subantarctic soils represent a largely unexplored component of the environmental resistome, particularly beta-lactamases, whose diversity, structural features, and biogeographic patterns remain poorly resolved. Here, we applied an integrative metagenomic approach combining sequence-, structure-, and function-based similarity to systematically identify putative beta-lactamase orthologs across an extensive collection of Antarctic and Subantarctic soil metagenomes. We detected multiple beta-lactamase classes and families, with a predominance of class A serine beta-lactamases and subclass B3 metallo-beta-lactamases. Several previously uncharacterized families and divergent variants were identified, many of which retain conserved catalytic architectures. Beta-lactamase diversity and relative abundance were strongly patterned across three major biogeographic clusters: Subantarctic islands, the Antarctic Peninsula and surrounding islands, and continental cold deserts, mirroring shifts in microbial community composition. The Antarctic Peninsula and maritime Antarctica exhibited the highest overall beta-lactamase abundance. Analysis of more than 3500 metagenome-assembled genomes indicated that most beta-lactamases were encoded by members of <i>p_Pseudomonadota</i> and <i>p_Bacteroidota</i>, with additional representatives distributed across other bacterial phyla. A subset was linked to mobile genetic elements, suggesting a latent but limited potential for horizontal gene transfer. Together, these findings reveal a geographically organized and compositionally diverse repertoire of beta-lactamases in (sub)Antarctic soils, underscoring the evolutionary persistence of conserved catalytic frameworks in cold environments and highlighting the contribution of remote ecosystems to global resistome diversity.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70118"},"PeriodicalIF":0.0,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218116","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}
iMetaOmicsPub Date : 2026-07-03eCollection Date: 2026-09-01DOI: 10.1002/imo2.70112
Muhammad Asif, Hazrat Bilal, Min Xiao, Lei Dong, Wen-Jun Li
{"title":"Microbiome-mediated plant-soil feedbacks as a tool for resilient agriculture.","authors":"Muhammad Asif, Hazrat Bilal, Min Xiao, Lei Dong, Wen-Jun Li","doi":"10.1002/imo2.70112","DOIUrl":"10.1002/imo2.70112","url":null,"abstract":"<p><p>Conventional agricultural intensification has eroded the biological foundations of productive soil by disrupting the reciprocal interactions, plant-soil feedback (PSF), through which plants actively shape and are continuously shaped by the soil microbiome. Although the molecular mechanisms governing PSF direction are increasingly well-characterized, deliberate PSF management as a practical tool for resilient crop production remains underdeveloped. This is largely because no integrative framework has translated these ecological insights into state-contingent, field-deployable decision rules. This review addresses that gap by first synthesizing the molecular basis of microbiome assembly, encompassing host genetic control of root exudate chemistry, receptor-mediated microbial recognition, and the bidirectional chemical dialogue between plant and rhizosphere. Building from this mechanistic foundation, we move beyond cataloging mechanisms to present a novel, integrative three-pillar management framework for actively steering PSF. This framework operationalizes PSF management by strategically combining: (i) engineering the plant partner (leveraging genetics to recruit beneficial microbiomes), (ii) managing the soil habitat (using agronomic practices to engineer suppressive ecological legacies), and (iii) deploying advanced microbial consortia. Critically, we argue that the recent meta-omics revolution, integrating metagenomics, metatranscriptomics, metaproteomics, and metabolomics, is the enabling technology that transforms this framework from a conceptual model into a quantifiable, diagnosable, and agriculturally deployable system. Multi-omics tools provide the empirical foundation for diagnosing soil feedback states, monitoring intervention outcomes, and building predictive models. By bridging the lab-field gap and evaluating key translational challenges, this review provides a coherent, actionable roadmap for harnessing PSF to achieve cultivated resilience in modern agriculture.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70112"},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218064","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}
{"title":"A multiplex interactome of Ebola virus proteins reveals TM9SF2 as a cell-surface attachment factor that promotes viral entry.","authors":"Limin Shang, Shouwen Du, Yuchen Liu, Letian Li, Xi Wu, Yanzhi Yuan, Chaozhi Jin, Qingkun Mi, Yuhang Wang, Xiaoshuang Shi, Jiamin Wang, Guoqing Zhang, Yidan Ma, Weijin Huang, Jigang Wang, Jian Wang, Chang Li","doi":"10.1002/imo2.70116","DOIUrl":"10.1002/imo2.70116","url":null,"abstract":"<p><p>The high lethality of the Ebola virus (EBOV) underscores the critical need to understand its molecular lifecycle. Here, we systematically mapped EBOV-host interactions using affinity purification-mass spectrometry (AP-MS) and proximity labeling, generating a comprehensive protein-protein interaction (PPI) network, of which 1728 are high-confidence core PPIs involving nine EBOV proteins and 914 human interactors. Notably, we identified transmembrane 9 superfamily member 2 (TM9SF2) as a novel attachment factor that facilitates EBOV glycoprotein (GP)-mediated entry. Mechanistic studies demonstrated that the receptor-binding domain (RBD) of EBOV GP associates with the extracellular domain (ECD) of TM9SF2, enhancing cellular adhesion and viral attachment. Moreover, the anti-TM9SF2 antibodies effectively attenuated EBOV GP-mediated pseudovirus entry and infection in vitro. Additionally, <i>Tm9sf2</i> <sup><i>+/</i></sup> <i><sup>-</sup></i> knockout mice exhibited significantly reduced susceptibility to EBOV pseudoviruses. These findings provide critical insights into EBOV-host interactions and establish TM9SF2 as a promising therapeutic target for antiviral intervention.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 3","pages":"e70116"},"PeriodicalIF":0.0,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218080","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}
iMetaOmicsPub Date : 2026-06-23eCollection Date: 2026-06-01DOI: 10.1002/imo2.70102
Ting Liang, Wuwu Xu, Hu Fang, Lu Fu, Dashi Deng, Chenchen Li, Lisha Liu, Dongdong Tang, Huancheng Yang, Fang Liu, Xing Xiong, Guangzhi Li, Song Wu, Tao Tao
{"title":"Integrin α5β1-mediated multicellular crosstalk in the tumor microenvironment drives bladder cancer progression and reveals targetable vulnerabilities.","authors":"Ting Liang, Wuwu Xu, Hu Fang, Lu Fu, Dashi Deng, Chenchen Li, Lisha Liu, Dongdong Tang, Huancheng Yang, Fang Liu, Xing Xiong, Guangzhi Li, Song Wu, Tao Tao","doi":"10.1002/imo2.70102","DOIUrl":"10.1002/imo2.70102","url":null,"abstract":"<p><p>Bladder cancer (BCa) progression is driven by complex interactions within the tumor microenvironment, yet the underlying multicellular communication networks remain poorly defined. Here, we integrated bulk, single-cell, and spatial transcriptomic data with multiplexed immunofluorescence to construct a comprehensive cellular atlas across normal urothelium, precancerous lesions, and progressive BCa. We identified a stemness-associated malignant epithelial population (Cluster 1_SDC1), a prognostically unfavorable subset of POSTN+ myofibroblastic cancer-associated fibroblasts (mCAFs), and immunosuppressive monocytic myeloid-derived suppressor cells (M-MDSCs), all enriched in high-grade tumors. Spatial mapping revealed a coordinated signaling cascade wherein POSTN+ mCAFs and M-MDSCs co-localize and engage integrin α5β1 on tip endothelial cells through FN1 and NAMPT, collectively driving angiogenesis. In turn, tip endothelial cells reinforce tumor stemness through downstream COL4A1/2-SDC1 signaling. Therapeutically, targeting integrin α5β1 with RGD peptide suppressed tumor growth and vascularization, while its combination with hydrogel-based delivery and immune checkpoint blockade elicited broad-spectrum antitumor responses. These findings uncover a spatially coordinated immune-stroma-tumor signaling cascade and establish integrin α5β1 as a central therapeutic target, providing a rationale for stroma-directed combination strategies in progressive BCa.</p>","PeriodicalId":521007,"journal":{"name":"iMetaOmics","volume":"3 2","pages":"e70102"},"PeriodicalIF":0.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218076","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}