Development of Human Vaginal Epithelial Organoids as a Model for Epithelial Homeostasis and Host-Microbe Interactions

While the vaginal epithelium is essential for female reproductive health, the mechanisms governing its homeostasis and diseases have remained elusive, in part due to the lack of model systems that recapitulate the stem cell niche of the native tissue. Here, we establish human vaginal epithelial organoids (hVEOs) guided by scRNA-seq of primary tissue. hVEOs faithfully recapitulate key in vivo characteristics, including a stratified squamous epithelium, estrogen response, and cellular lineage consistency. The transcriptional consistency between hVEOs and native tissue was validated at single-cell resolution. Furthermore, the infection of hVEOs with Candida demonstrated the model's capacity to recapitulate specific inflammatory responses, confirming its utility for host-pathogen research. In summary, this study provides a robust, physiologically relevant model to dissect the molecular pathways of human vaginal homeostasis and disease, facilitating the definition of pathogenic mechanisms and the screening of novel therapeutics.