{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:53:01Z","timestamp":1793904781607,"version":"4.8.0"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T00:00:00Z","timestamp":1679788800000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971361"],"award-info":[{"award-number":["81971361"]}],"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":["82173188"],"award-info":[{"award-number":["82173188"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The mechanism underlying cervical carcinogenesis that is mediated by persistent human papillomavirus (HPV) infection remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>Here, for the first time, we deciphered both the temporal transition and spatial distribution of cellular subsets during disease progression from normal cervix tissues to precursor lesions to cervical cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials &amp; Methods<\/jats:title><jats:p>We generated scRNA\u2010seq profiles and spatial transcriptomics data from nine patient samples, including two HPV\u2010negative normal, two HPV\u2010positive normal, two HPV\u2010positive HSIL and three HPV\u2010positive cancer samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We not only identified three \u2018HPV\u2010related epithelial clusters\u2019 that are unique to normal, high\u2010grade squamous intraepithelial lesions (HSIL) and cervical cancer tissues but also discovered node genes that potentially regulate disease progression. Moreover, we observed the gradual transition of multiple immune cells that exhibited positive immune responses, followed by dysregulation and exhaustion, and ultimately established an immune\u2010suppressive microenvironment during the malignant program. In addition, analysis of cellular interactions further verified that a \u2018homeostasis\u2010balance\u2010malignancy\u2019 change occurred within the cervical microenvironment during disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We for the first time presented a spatiotemporal atlas that systematically described the cellular heterogeneity and spatial map along the four developmental steps of HPV\u2010related cervical oncogenesis, including normal, HPV\u2010positive normal, HSIL and cancer. We identified three unique HPV\u2010related clusters, discovered critical node genes that determined the cell fate and uncovered the immune remodeling during disease escalation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Together, these findings provided novel possibilities for accurate diagnosis, precise treatment and prognosis evaluation of patients with precancer and cervical cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1219","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T05:00:40Z","timestamp":1679893240000},"source":"Crossref","is-referenced-by-count":123,"title":["Spatiotemporally deciphering the mysterious mechanism of persistent HPV\u2010induced malignant transition and immune remodelling from HPV\u2010infected normal cervix, precancer to cervical cancer: Integrating single\u2010cell RNA\u2010sequencing and spatial 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