{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:36:29Z","timestamp":1772638589722,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702712"],"award-info":[{"award-number":["81702712"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Actinic keratosis (AK) represents an intraepidermal malignant neoplasm with the proliferation of atypical keratinocytes. AK lesions are regarded as early in situ squamous cell carcinomas (SCCs) having the potential to progress into invasive SCC (iSCC) and metastasize, causing death. This study aimed to investigate the heterogeneity of keratinocytes and how this heterogeneity promoted AK development and progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employed single\u2010cell RNA sequencing (scRNA\u2010seq) to examine the heterogeneity of keratinocytes and dermal fibroblast clusters in AKs and adjacent normal skins. Cell clustering, pseudotime trajectory construction, gene ontology enrichment analysis, transcription factor network analysis, and cell\u2013cell communication were used to investigate the heterogeneity of keratinocytes in AK. The cellular identity and function were verified by immunohistochemical and immunofluorescence staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using scRNA\u2010seq, we revealed 13 keratinocyte subgroups (clusters 0\u201312) in AK tissues and characterized 2 AK\u2010specific clusters. Cluster 9 displayed high levels of IL1R2 and WFDC2, and cluster 11 showed high levels of FADS2 and FASN. The percentages of cells in these two clusters significantly increased in AK compared with normal tissues. The existence and spatial localization of AK\u2010specific IL1R2+WFDC2+ cluster were verified by immunohistochemical and immunofluorescence staining. Functional studies indicated that the genes identified in the IL1R2+WFDC2+ cluster were crucial for epithelial cell proliferation, migration, and angiogenesis. Further immunofluorescent staining revealed the interactions between AK\u2010specific keratinocytes and secretory\u2010papillary fibroblasts mainly through ANGPTL4\u2010ITGA5 signalling pathway rarely seen in normal tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings of this study might help better understand AK pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.19289","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T05:26:25Z","timestamp":1687757185000},"page":"2273-2283","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Single\u2010cell <scp>RNA<\/scp>\u2010seq reveals actinic keratosis\u2010specific keratinocyte subgroups and their crosstalk with secretory\u2010papillary fibroblasts"],"prefix":"10.1111","volume":"37","author":[{"given":"Jun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Dermatology, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology (HUST)  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology (HUST)  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shumin","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology (HUST)  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology (HUST)  Wuhan 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