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However, the microenvironmental ecosystem of PMP, particularly in metastatic lesions, remains poorly understood. Here, we integrated single\u2010cell RNA sequencing, whole\u2010exome sequencing, bulk RNA sequencing, and histopathologic validation to construct a high\u2010resolution atlas of primary and paired metastatic tumors. Epithelial cells showed distinct functional states, including a TFF3\n +<\/jats:sup>\n mucus secretion\u2010associated state and a MACC1\n +<\/jats:sup>\n malignant\u2010associated state. Metastatic lesions showed coordinated microenvironmental reprogramming, including POSTN\n +<\/jats:sup>\n fibrosis\u2010associated fibroblasts, CXCL5\n +<\/jats:sup>\n macrophages linked to local immunosuppressive signaling, and immune exclusion associated with a collagen\u2010rich stromal barrier. We also observed extensive lipid metabolic activity and identified a candidate pro\u2010angiogenic network involving POSTN\n +<\/jats:sup>\n fibroblasts, RSPO3\n +<\/jats:sup>\n pericytes, and endothelial cells, potentially mediated by VEGFA\u2013VEGFR2 signaling. Retrospective observations from three recurrent PMP cases further suggested the potential therapeutic value of VEGFR2\u2010targeted anti\u2010angiogenic therapy. Overall, this study provides a comprehensive single\u2010cell transcriptomic atlas of PMP and a resource for developing novel and combination therapeutic strategies.\n <\/jats:p>","DOI":"10.1002\/advs.202523760","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:56:04Z","timestamp":1785153364000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Transcriptomic Analysis of Tumor Heterogeneity and the Microenvironment in Pseudomyxoma Peritonei"],"prefix":"10.1002","volume":"13","author":[{"given":"Xi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Geriatric Surgery Xiangya Hospital Central South University Changsha Hunan People's Republic of China"},{"name":"National Clinical Research Center for Geriatric Disorders Changsha Hunan People's Republic of China"},{"name":"Department of General Surgery Xiangya Hospital Central South University 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