Lineage-Specific Sex-Biased Transcriptional Programs in Healthy Human Truncal Skin Revealed by Single-Cell Transcriptomics
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: Genes
Authors: Yu Yang, Honghao Yu, Binbin Lai
Institutions: Peking University, Peking University First Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W7147729258
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