{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:53:44Z","timestamp":1791384824534,"version":"4.3.3"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61372142"],"award-info":[{"award-number":["61372142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hepatic angiomyolipoma (HAML) is a rare variant of perivascular epithelioid cell neoplasms (PEComas). Unlike its more common renal angiomyolipoma (RAML), the unique spatial microenvironment of HAML and its specific progression mechanisms remain poorly characterized. Here, we integrated single\u2010nucleus RNA\u2010sequencing and spatial transcriptomics from three sporadic HAML cases. We mapped functionally heterogeneous PEComas subpopulations and their localized tissue niches. Transcriptomic alignment and spatial colocalization demonstrated a high similarity between endothelial cells and a subset of PEComas, supporting a potential transition trajectory. Furthermore, spatial intercellular communication analysis identified an endothelial\u2010derived PDGFD\u2010PDGFRB axis. We propose that this paracrine signaling engages downstream Ras cascades to sustain localized autophagic flux in adjacent PEComas, potentially acting as a compensatory survival mechanism parallel to intrinsic TSC\u2010mTOR defects. While definitive in\u00a0vivo functional fate\u2010mapping and perturbation studies are requisite, this multi\u2010omics atlas provides a novel spatial framework for HAML pathogenesis and highlights the endothelial\u2010PEComa signaling network as a potential therapeutic vulnerability.<\/jats:p>","DOI":"10.1111\/cas.70550","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:09:05Z","timestamp":1791382145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mapping the Tissue Architecture and Endothelial\u2010\n                    <scp>PEC<\/scp>\n                    Network in\n                    <scp>HAML<\/scp>\n                    Using Single\u2010Cell and Spatial Transcriptomics"],"prefix":"10.1111","author":[{"given":"Xinyang","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Department of General Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Guo","sequence":"additional","affiliation":[{"name":"Heilongjiang Province Key Laboratory of Molecular Oncology Harbin Medical University Cancer Hospital  Harbin China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Tie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Department of General Surgery The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Heilongjiang Province Key Laboratory of Molecular Oncology Harbin Medical University Cancer Hospital  Harbin China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyu","family":"Li","sequence":"additional","affiliation":[{"name":"Heilongjiang Province Key Laboratory of Molecular Oncology Harbin Medical University Cancer Hospital  Harbin China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingkai","family":"Liu","sequence":"additional","affiliation":[{"name":"Heilongjiang Province Key Laboratory of Molecular Oncology Harbin Medical University Cancer Hospital  Harbin China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohang","family":"Sun","sequence":"additional","affiliation":[{"name":"Heilongjiang Province Key Laboratory of Molecular Oncology Harbin Medical University Cancer Hospital  Harbin China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Heilongjiang Province Key Laboratory of Molecular Oncology Harbin Medical University Cancer Hospital  Harbin China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Geng","sequence":"additional","affiliation":[{"name":"Heilongjiang Province Key Laboratory of Molecular Oncology Harbin Medical University Cancer Hospital  Harbin China"},{"name":"Science and Technology Research Center Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7657-6900","authenticated-orcid":false,"given":"Yingjian","family":"Liang","sequence":"additional","affiliation":[{"name":"Heilongjiang Province Key Laboratory of Molecular Oncology Harbin Medical University Cancer Hospital  Harbin China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery Harbin Medical University Cancer Hospital  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"issue":"6","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/his.15405","article-title":"Risk Prediction Criteria for the Primary Hepatic Perivascular Epithelioid Cell Tumour Family, Including Angiomyolipoma: Analysis of 132 Cases With a Literature Review","volume":"86","author":"Yoo Y.","year":"2025","journal-title":"Histopathology"},{"issue":"5","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"812","DOI":"10.3748\/wjg.14.812","article-title":"Coincidence of Hepatocelluar Carcinoma and Hepatic Angiomyolipomas in Tuberous Sclerosis Complex: A Case Report","volume":"14","author":"Yang B.","year":"2008","journal-title":"World Journal of Gastroenterology"},{"issue":"5","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/his.12551","article-title":"Alterations of the mTOR Pathway in Hepatic Angiomyolipoma With Emphasis on the Epithelioid Variant and Loss of Heterogeneity of TSC1\/TSC2","volume":"66","author":"Huang S. C.","year":"2015","journal-title":"Histopathology"},{"issue":"4","key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/his.15005","article-title":"TSC2 Inactivation, Low Mutation Burden and High Macrophage Infiltration Characterise Hepatic Angiomyolipomas","volume":"83","author":"Giannikou K.","year":"2023","journal-title":"Histopathology"},{"issue":"7","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1080\/15548627.2020.1783119","article-title":"Regulation and Repurposing of Nutrient Sensing and Autophagy in Innate Immunity","volume":"17","author":"Sanchez\u2010Garrido J.","year":"2021","journal-title":"Autophagy"},{"issue":"17","key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"5295","DOI":"10.1158\/1078-0432.CCR-19-0288","article-title":"Role of Chemotherapy, VEGFR Inhibitors, and mTOR Inhibitors in Advanced Perivascular Epithelioid Cell Tumors (PEComas)","volume":"25","author":"Sanfilippo R.","year":"2019","journal-title":"Clinical Cancer Research"},{"key":"e_1_2_13_8_1","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms14049","article-title":"Massively Parallel Digital Transcriptional Profiling of Single Cells","volume":"8","author":"Zheng G. 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P.","year":"2014","journal-title":"Science"},{"issue":"11","key":"e_1_2_13_14_1","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: Single\u2010Cell Regulatory Network Inference and Clustering","volume":"14","author":"Aibar S.","year":"2017","journal-title":"Nature Methods"},{"issue":"1","key":"e_1_2_13_15_1","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and Analysis of Cell\u2010Cell Communication Using CellChat","volume":"12","author":"Jin S.","year":"2021","journal-title":"Nature Communications"},{"issue":"51","key":"e_1_2_13_16_1","doi-asserted-by":"crossref","first-page":"eabg3750","DOI":"10.1126\/sciadv.abg3750","article-title":"Comprehensive Analysis of Spatial Architecture in Primary Liver Cancer","volume":"7","author":"Wu R.","year":"2021","journal-title":"Science Advances"},{"issue":"5","key":"e_1_2_13_17_1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jhep.2020.05.039","article-title":"Single\u2010Cell Transcriptomic Architecture and Intercellular Crosstalk of Human Intrahepatic Cholangiocarcinoma","volume":"73","author":"Zhang M.","year":"2020","journal-title":"Journal of Hepatology"},{"issue":"2","key":"e_1_2_13_18_1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.cell.2020.11.041","article-title":"Single\u2010Cell Landscape of the Ecosystem in Early\u2010Relapse Hepatocellular Carcinoma","volume":"184","author":"Sun Y.","year":"2021","journal-title":"Cell"},{"issue":"10","key":"e_1_2_13_19_1","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1164\/rccm.201912-2445OC","article-title":"Single\u2010Cell Transcriptomic Analysis Identifies a Unique Pulmonary Lymphangioleiomyomatosis Cell","volume":"202","author":"Guo M.","year":"2020","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"issue":"5","key":"e_1_2_13_20_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3892\/ijo.2022.5422","article-title":"A Multi\u2010Omics Study of Diagnostic Markers and the Unique Inflammatory Tumor Micro\u2010Environment Involved in Tuberous Sclerosis Complex\u2010Related Renal Angiomyolipoma","volume":"61","author":"Wang Z.","year":"2022","journal-title":"International Journal of Oncology"},{"key":"e_1_2_13_21_1","doi-asserted-by":"crossref","first-page":"15816","DOI":"10.1038\/ncomms15816","article-title":"The Genomic Landscape of Tuberous Sclerosis Complex","volume":"8","author":"Martin K. R.","year":"2017","journal-title":"Nature Communications"},{"issue":"12","key":"e_1_2_13_22_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21124271","article-title":"EMT and EndMT: Emerging Roles in Age\u2010Related Macular Degeneration","volume":"21","author":"Shu D. Y.","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"issue":"6","key":"e_1_2_13_23_1","first-page":"830","article-title":"Perivascular Epithelioid Cell Tumours of the Genitourinary Tract: Clinicopathological Features and Molecular Landscape","volume":"83","author":"Yaprak Bayrak B.","year":"2026","journal-title":"Histopathology"},{"issue":"2","key":"e_1_2_13_24_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1097\/PAS.0000000000000133","article-title":"Perivascular Epithelioid Cell Neoplasm (PEComa) of the Gynecologic Tract: Clinicopathologic and Immunohistochemical Characterization of 16 Cases","volume":"38","author":"Schoolmeester J. K.","year":"2014","journal-title":"American Journal of Surgical Pathology"},{"issue":"2","key":"e_1_2_13_25_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00428-007-0509-1","article-title":"PEComas: The Past, the Present and the Future","volume":"452","author":"Martignoni G.","year":"2008","journal-title":"Virchows Archiv"},{"issue":"6","key":"e_1_2_13_26_1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.5858\/2001-125-0751-RA","article-title":"Renal Angiomyolipoma: Further Immunophenotypic Characterization of an Expanding Morphologic Spectrum","volume":"125","author":"Stone C. H.","year":"2001","journal-title":"Archives of Pathology & Laboratory Medicine"},{"key":"e_1_2_13_27_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1196\/annals.1339.045","article-title":"The Role of Tuberin in Cellular Differentiation: Are B\u2010Raf and MAPK Involved","volume":"1059","author":"Karbowniczek M.","year":"2005","journal-title":"Annals of the New York Academy of Sciences"},{"issue":"19","key":"e_1_2_13_28_1","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2021108863","article-title":"Autophagy in Major Human Diseases","volume":"40","author":"Klionsky D. J.","year":"2021","journal-title":"EMBO Journal"},{"issue":"11","key":"e_1_2_13_29_1","first-page":"3329","article-title":"Autophagy Regulates Adipose Mass and Differentiation in Mice","volume":"119","author":"Singh R.","year":"2009","journal-title":"Journal of Clinical Investigation"},{"issue":"1","key":"e_1_2_13_30_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cell.2017.06.009","article-title":"RAS Proteins and Their Regulators in Human Disease","volume":"170","author":"Simanshu D. K.","year":"2017","journal-title":"Cell"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70550","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70550","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:09:09Z","timestamp":1791382149000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":29,"alternative-id":["10.1111\/cas.70550"],"URL":"https:\/\/doi.org\/10.1111\/cas.70550","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"2026-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cas.70550"}}