{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:08:56Z","timestamp":1790690936687,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC3407700"],"award-info":[{"award-number":["2024YFC3407700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2504700"],"award-info":[{"award-number":["2022YFC2504700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82422058"],"award-info":[{"award-number":["82422058"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470959"],"award-info":[{"award-number":["32470959"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470715"],"award-info":[{"award-number":["32470715"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1455300"],"award-info":[{"award-number":["23ZR1455300"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pancreatic stellate cells (PSCs) contribute to pancreatic ductal adenocarcinoma (PDAC) progression and therapeutic resistance, yet their detailed functions remain unclear. This study combined RNA sequencing and assay for transposase\u2010accessible chromatin using sequencing (ATAC\u2010seq) on sorted PSCs from adjacent normal and PDAC tissues to investigate their transcriptional and epigenetic activation. PSCs heterogeneity and functions are characterized through bulk, single\u2010cell, and spatial transcriptomes, as well as in situ sequencing. The clinical relevance of PSCs in immunotherapy is assessed using an in\u2010house immune\u2010checkpoint blockade (ICB) treatment cohort. Findings showed that stress and hypoxia signaling activated PSCs in PDAC. Three common PSCs (CPSCs) and four tumor\u2010associated PSCs (TPSCs) are identified, each with distinct functions. CPSCs differentiated into\n                    <jats:italic>CCL19<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    TPSCs in immune\u2010enriched regions,\n                    <jats:italic>MYH11<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    TPSCs in the stromal region, and\n                    <jats:italic>PLXDC1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    TPSCs, which exhibited cancer\u2010associated myofibroblasts (myCAFs) phenotype linked to poor prognosis. Notably,\n                    <jats:italic>PLXDC1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    TPSCs, located near aggressive\n                    <jats:italic>LRRC15<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    myCAFs and\n                    <jats:italic>SPP1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    macrophages, formed a desmoplastic and immunosuppressive niche around the tumor boundary, promoting CD8 T cell exhaustion. Single\u2010cell transcriptomics of PDAC patients treated with ICB revealed that\n                    <jats:italic>PLXDC1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    TPSCs correlated with poor immunotherapy efficacy. Overall, this study provides key insights into PSCs in PDAC and potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1002\/advs.202415756","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T03:19:11Z","timestamp":1742181551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["<i>PLXDC1<\/i>\n                    <sup>+<\/sup>\n                    Tumor\u2010Associated Pancreatic Stellate Cells Promote Desmoplastic and Immunosuppressive Niche in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Yanhua","family":"Du","sequence":"first","affiliation":[{"name":"Center for Immune\u2010Related Diseases at Shanghai Institute of Immunology Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200001 China"},{"name":"Shanghai Jiao Tong University School of Medicine\u2010Yale Institute for Immune Metabolism, State Key Laboratory of Systems Medicine for Cancer Shanghai Jiao Tong University School of Medicine  Shanghai 20025 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Immune\u2010Related Diseases at Shanghai Institute of Immunology Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pancreatic\u2010biliary Surgery Changzheng Hospital Naval Medical University  Shanghai 200003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Immune\u2010Related Diseases at Shanghai Institute of Immunology Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglan","family":"You","sequence":"additional","affiliation":[{"name":"Center for Immune\u2010Related Diseases at Shanghai Institute of Immunology Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Immune\u2010Related Diseases at Shanghai Institute of Immunology Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Immune\u2010Related Diseases at Shanghai Institute of Immunology Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200001 China"},{"name":"Shanghai Jiao Tong University School of Medicine\u2010Yale Institute for Immune Metabolism, State Key Laboratory of Systems Medicine for Cancer Shanghai Jiao Tong University School of Medicine  Shanghai 20025 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Hebei Key Laboratory of General Surgery for Digital Medicine Affiliated Hospital of Hebei University  Baoding 071000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Alinejad\u2010Rokny","sequence":"additional","affiliation":[{"name":"UNSW BioMedical Machine Learning Lab (BML) School of Biomedical Engineering UNSW Sydney  Sydney NSW 2052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujie","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Hebei Key Laboratory of General Surgery for Digital Medicine Affiliated Hospital of Hebei University  Baoding 071000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Pancreatic\u2010biliary Surgery Changzheng Hospital Naval Medical University  Shanghai 200003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duowu","family":"Zou","sequence":"additional","affiliation":[{"name":"Center for Immune\u2010Related Diseases at Shanghai Institute of Immunology Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-4710","authenticated-orcid":false,"given":"Youqiong","family":"Ye","sequence":"additional","affiliation":[{"name":"Center for Immune\u2010Related Diseases at Shanghai Institute of Immunology Department of Gastroenterology Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200001 China"},{"name":"Shanghai Jiao Tong University School of Medicine\u2010Yale Institute for Immune Metabolism, State Key Laboratory of Systems Medicine for Cancer Shanghai Jiao Tong University School of Medicine  Shanghai 20025 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i43.4846"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123770"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.4.535"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100617-062855"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0601"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0644"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.08.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.127"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142162"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2019.01.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.08.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.06.047"},{"key":"e_1_2_9_13_1","first-page":"391","volume":"28","author":"Gundewar C.","year":"2015","journal-title":"Ann. Gastroenterol."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.05.074"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03549-5"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106988"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3823"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108505"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.43.1.128"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.934783"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2022.100340"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01141-9"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01139-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36560-7"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29366-6"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.01.010"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1496"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-2994"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.11.017"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe6474"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0667-5"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0171-6_6"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0815-z"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00218"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040319"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20162024"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05272-1"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0000000000001464"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.05.051"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0195-y"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2018.11.005"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06654-8"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv325"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0336-3"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00692-9"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2023.02.004"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202415756","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202415756","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202415756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:47:33Z","timestamp":1788529653000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202415756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":50,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/advs.202415756"],"URL":"https:\/\/doi.org\/10.1002\/advs.202415756","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"assertion":[{"value":"2024-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2415756"}}