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Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase\u2013AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor \u03baB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.<\/jats:p>","DOI":"10.1126\/sciadv.adl3511","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T18:00:27Z","timestamp":1715796027000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":47,"title":["Cervical extracellular matrix hydrogel optimizes tumor heterogeneity of cervical squamous cell carcinoma organoids"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4608-0521","authenticated-orcid":true,"given":"Haonan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5165-3679","authenticated-orcid":true,"given":"Haoyuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3911-4609","authenticated-orcid":true,"given":"Weichu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8102-6766","authenticated-orcid":true,"given":"Yan","family":"Hai","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9098-9329","authenticated-orcid":true,"given":"Yihuan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Jinan University, Guangzhou 510280, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuru","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, The Sixth Affiliated Hospital, South China University of Technology, Foshan 528200, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yefei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Affiliated Foshan Maternity &amp; 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