Molecular stratification of human fetal vaginal epithelium by spatial transcriptome analysis

The human vaginal epithelium is a crucial component in numerous reproductive processes and serves as a vital protective barrier against pathogenic invasion. Despite its significance, a comprehensive exploration of its molecular profiles, including molecule expression and distribution across its multiple layers, remains elusive. In our study, we undertook a spatial transcriptomic analysis within the vaginal wall of human fetuses to fill this knowledge gap. We successfully categorized vaginal epithelium into four distinct zones based on their transcriptomic profiles and anatomical features. This approach unveiled unique transcriptomic signatures within these regions, allowing us to identify differentially expressed genes and uncover novel markers for distinct regions of the vaginal epithelium. Additionally, our findings have highlighted the varied expression of KRT genes across different zone of the vaginal epithelium, with a gradual shift in expression patterns observed from the basal layer to the surface/superficial layer. This suggests a potential differentiation trajectory of human vaginal epithelium, shedding light on the dynamic nature of this tissue. Furthermore, abundant biological processes were found to be enriched in the basal zone by the KEGG pathway analysis, indicating an active state of the basal zone cells. Subsequently, the expression of latent stem cell markers in the basal zone were identified. In summary, our research provides crucial understanding of human vaginal epithelial cells and the complex mechanisms of the vaginal mucosa, with potential applications in vaginal reconstruction and drug delivery, making this atlas a valuable tool for future research in women’s health and reproductive medicine.