{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T13:02:14Z","timestamp":1775134934623,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Project of China","award":["2023YFC3404400"],"award-info":[{"award-number":["2023YFC3404400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Sex differences influence skin physiology, immune regulation, and disease susceptibility, but the cellular organization of sex-biased transcriptional programs in healthy human skin remains incompletely defined. We aimed to define sex-associated differences in cellular composition and gene expression in healthy adult truncal skin at single-cell resolution. Methods: We constructed a sex-resolved single-cell transcriptomic atlas of healthy human truncal skin by integrating scRNA-seq data from 12 donors (5 males, 7 females). After quality control, 107,967 cells were classified into 14 major cell types. Sex-associated differences were assessed using donor-level pseudo-bulk analyses at both whole-skin and cell-type-resolved levels. Results: The cellular composition was conserved between sexes, with significant differences in mast cells and regulatory T cells. Whole-skin pseudo-bulk analysis identified distinct male-biased and female-biased transcriptional programs. Male-biased signals were linked to extracellular matrix organization and immune responses, while female-biased signals involved ion transport and neuromodulation. Cell-type-resolved analysis revealed that most sex-biased genes were lineage-specific, with minimal cross-lineage sharing. Conclusions: Sexual dimorphism in healthy human truncal skin is encoded through lineage-structured transcriptional regulation rather than broad compositional changes, providing a framework for understanding sex-biased skin homeostasis and disease susceptibility.<\/jats:p>","DOI":"10.3390\/genes17040415","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lineage-Specific Sex-Biased Transcriptional Programs in Healthy Human Truncal Skin Revealed by Single-Cell Transcriptomics"],"prefix":"10.3390","volume":"17","author":[{"given":"Yu","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China"},{"name":"Department of Dermatology and Venereology, Peking University First Hospital, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honghao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Peking University First Hospital, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binbin","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China"},{"name":"Department of Dermatology and Venereology, Peking University First Hospital, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41576-018-0083-1","article-title":"The Role of Sex in the Genomics of Human Complex Traits","volume":"20","author":"Khramtsova","year":"2019","journal-title":"Nat. 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