{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:28:40Z","timestamp":1790728120621,"version":"4.1.0"},"reference-count":93,"publisher":"Wiley","issue":"32","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["444776998"],"award-info":[{"award-number":["444776998"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["314061271\u2010TRR 205"],"award-info":[{"award-number":["314061271\u2010TRR 205"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["570979695"],"award-info":[{"award-number":["570979695"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82400925"],"award-info":[{"award-number":["82400925"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M762878"],"award-info":[{"award-number":["2024M762878"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2012_A103"],"award-info":[{"award-number":["2012_A103"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2015_A228"],"award-info":[{"award-number":["2015_A228"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["and 2019_A104"],"award-info":[{"award-number":["and 2019_A104"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["694913"],"award-info":[{"award-number":["694913"]}],"id":[{"id":"10.13039\/100010663","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":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aldosterone\u2010producing adenomas (APAs) and micronodules (APMs) are histopathological lesions that can cause a prevalent form of secondary hypertension called primary aldosteronism. Using integrated single\u2010cell\/nucleus and spatial transcriptomics, it demonstrates substantial heterogeneity between APMs and APAs, alongside an immunosuppressive tumor microenvironment in APAs. Pseudotime analyses reveal two distinct evolutionary trajectories in APAs: a direct progression from zona glomerulosa cells to APAs, observed specifically in\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    \u2010mutated tumors, and a stepwise path from zona glomerulosa cells to APMs and then to APAs, present in both\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    \u2010mutated APAs and APAs without\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    mutations. Within\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    \u2010mutated APAs, we identified two distinct cellular states with different differentiation potentials: a progenitor\u2010like state (high differentiation potential) and a mature state (low differentiation potential). This uncovered a spectrum of molecular and functional shifts during APA progression involving pathways of oxidative stress (including mechanisms leading to cell death by ferroptosis) and focal adhesion (influenced by cell density). In vitro studies in human adrenal cells demonstrate that\n                    <jats:italic>TAZ<\/jats:italic>\n                    activation regulates ferroptosis sensitivity in response to cell density changes. The findings enhance understanding of the transcriptional diversity in APMs and APAs and elucidate complex molecular alterations underlying APA pathogenesis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202505410","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T10:02:09Z","timestamp":1768989729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Integrated Transcriptomics Reveals Evolutionary Trajectories and Cell Density\u2010Dependent Mechanisms in Aldosterone\u2010Producing Adenomas"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhuolun","family":"Sun","sequence":"first","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV Klinikum der Universit\u00e4t M\u00fcnchen Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  80336 Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changying","family":"Jing","sequence":"additional","affiliation":[{"name":"Institute of Diabetes and Regeneration Research Helmholtz Munich Neuherberg, Germany, German Center for Diabetes Research (DZD) Neuherberg, Germany Munich Medical Research School Ludwig\u2010Maximilians\u2010Universit\u00e4t  80539 Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Tetti","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV Klinikum der Universit\u00e4t M\u00fcnchen Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  80336 Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV Klinikum der Universit\u00e4t M\u00fcnchen Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  80336 Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Wei","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV Klinikum der Universit\u00e4t M\u00fcnchen Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  80336 Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxian","family":"Pang","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV Klinikum der Universit\u00e4t M\u00fcnchen Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  80336 Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reincke","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV Klinikum der Universit\u00e4t M\u00fcnchen Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  80336 Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-6444","authenticated-orcid":false,"given":"Tracy Ann","family":"Williams","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik IV Klinikum der Universit\u00e4t M\u00fcnchen Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  80336 Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_9_1_1","first-page":"1029","volume":"39","author":"Seccia T. M.","year":"2018","journal-title":"Endocr. Rev."},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2021.10.002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00210-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.01.052"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnad026"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.07.059"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4061"},{"key":"e_1_2_9_8_1","first-page":"1182","volume":"102","author":"Yamazaki Y.","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11465"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14041"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3285"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198785"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2695"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2716"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14349"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0377"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2550"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01498-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2017.32.3.332"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.16498"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01403-0"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ15-0642"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2010"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1505529112"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14177"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11086"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac394"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.21446"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e14357"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2421489122"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.20921"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.186205"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153716"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114395"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2021.111178"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1022-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI125505"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","DOI":"10.1177\/1533033820979685","volume":"19","author":"Zhou T.","year":"2020","journal-title":"Technol Cancer Res. Treat"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13619-020-00042-8"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32896-8"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103498"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03419"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316509"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.02.049"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2059170"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.5075"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201500374"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.107"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1722020115"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00991-2"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02865-0"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12459"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867328666210720143721"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.646523"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-256776"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.18388\/pb.2021_521"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-007-0436-0"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12109"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.10.014"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-122394"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0249"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4402"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-022-00198-w"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254257"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt484"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2020.05.004"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0691"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa484"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac408"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.124.23817"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.11.022"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_9_75_1","author":"Benjamin D.","year":"2019","journal-title":"bioRxiv"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01004"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_2_9_80_1","author":"Petukhov V.","year":"2022","journal-title":"bioRxiv"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33375-w"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn8367"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119976462"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7000-1_26"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3781"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2728"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.045"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-1284-2"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43120-6"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0903"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.16774"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202505410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202505410","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202505410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:43:21Z","timestamp":1781527401000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202505410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":93,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/advs.202505410"],"URL":"https:\/\/doi.org\/10.1002\/advs.202505410","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e05410"}}