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However, the molecular pathogenesis of IC\/BPS remains poorly understood, and few studies have provided comprehensive analyses. To elucidate the mechanisms underlying disease pathology, we performed integrated single-cell and spatial transcriptomic analyses of human bladder tissue. Comprehensive single-cell multiomics analyses have identified disease-specific alterations across multiple cell types. T helper 17 cells were significantly expanded in Hunner lesions and activated autoimmune and pro-inflammatory signaling pathways, suggesting a critical role in disease progression. Endothelial cells (ECs) shift from homeostatic (EC2) to pro-angiogenic inflammatory phenotypes (EC3), contributing to vascular remodeling. In the monocyte\u2013macrophage lineage, we identified macrophage 2 cells with pro-angiogenic features that engaged in vascular endothelial growth factor-mediated and tumor necrosis factor-mediated interactions that promoted pathological angiogenesis. Smooth muscle cells (SMCs) display notable phenotypic plasticity, transitioning from a contractile to a synthetic state in IC\/BPS tissues. Additionally, spatial transcriptomic analysis revealed upregulation of the EDN1\u2013EDNRA\/EDNRB signaling axis, suggesting a role for SMCs in bladder hypercontractility. Fibroblasts have emerged as key mediators of nociceptive signaling, with specific subpopulations enriched in neurotrophin-related pathways (for example, NTF3\u2013NTRK2\/NTRK3 and NGF\u2013SORT1) and showing active crosstalk with SMCs, potentially contributing to the development of chronic pain. Collectively, these findings delineate a complex stromal\u2013immune\u2013vascular network underlying the pathological remodeling and pain characteristics of IC\/BPS. Our study identified novel cellular players and intercellular signaling pathways that may be promising targets for therapeutic interventions.<\/jats:p>","DOI":"10.1038\/s12276-026-01768-2","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:46:19Z","timestamp":1783071979000},"page":"2235-2251","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated single-cell and spatial transcriptomics reveal stromal\u2013immune\u2013vascular crosstalk in patients with interstitial cystitis\/bladder pain syndrome"],"prefix":"10.1038","volume":"58","author":[{"given":"ByulA","family":"Jee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"IJun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheol","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon Jeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0511-4958","authenticated-orcid":false,"given":"Kyunghee","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hee","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inwoo","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Sun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Sung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Jin","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyong","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"1768_CR1","doi-asserted-by":"publisher","DOI":"10.1111\/luts.12532","volume":"16","author":"Y Homma","year":"2024","unstructured":"Homma, Y. et al. 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