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Nevertheless, the molecular mechanisms governing PPTC\u2010specific pathobiology remain elusive. Through high\u2010resolution single\u2010cell RNA sequencing analysis of 90234 cellular transcriptomes from 4 PPTC and 9 APTC clinical specimens, a phenotypically distinct cellular subpopulation (ITGA2\n                    <jats:sup>hi<\/jats:sup>\n                    \u2010PTC cells) mechanistically responsible for PPTC's distinct clinical behavior, is identified. By integrating PPTC\u2010derived organoid models with in vivo functional validation and multiplex immunohistochemistry, it is demonstrated that ITGA2 orchestrates dual oncogenic pathways: 1) augmentation of glycolytic flux and 2) induction of M2 macrophage polarization. These synergistic mechanisms fundamentally drive PPTC oncogenesis and metastatic progression. Cross\u2010validation across independent clinical cohorts consistently confirms the translational significance of these findings. Our multi\u2010omics characterization of PPTC\u2010specific cellular ecosystems and signaling cascades establishes a mechanistic framework for advancing diagnostic precision and targeted therapeutic development.\n                  <\/jats:p>","DOI":"10.1002\/advs.202504088","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T09:09:49Z","timestamp":1758618589000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Single\u2010Cell Transcriptomics Reveals ITGA2\u2010Mediated Metabolic Reprogramming and Immune Crosstalk in Pediatric Thyroid Carcinogenesis"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhi\u2010jun","family":"Zhan","sequence":"first","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3477-2194","authenticated-orcid":false,"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010da","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010han","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010xing","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe\u2010cheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010long","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"},{"name":"Clinical Research Center for Thyroid Disease in Hunan Province Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"Hunan Provincial Engineering Research Center for Thyroid and Related Diseases Treatment Technology Xiangya Hospital Central South University  Changsha Hunan 410008 China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3011-3359","authenticated-orcid":false,"given":"Peng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of General Surgery XiangYa Hospital Central South University  Changsha Hunan 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"e_1_2_10_1_1","first-page":"617","volume":"145","author":"Qian Z. 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