Decoding functional and developmental trajectories of tissue-resident uterine dendritic cells through integrative omics.

Uterine dendritic cells (uDCs) are critical for endometrial function, yet their origin and functional roles during the pre- and post-implantation periods in the human endometrium remain largely unknown. We hypothesize that distinct uDC subsets carry out specialized functions and that resident progenitor DCs generate these subtypes. Employing single-cell RNA sequencing (scRNA-seq) on uterine tissues collected across different menstrual phases and during early pregnancy, we identify several uDC subtypes, including resident progenitor DCs. CITE-seq was performed on endometrial single-cell suspensions to link surface protein expression with key genes identified by RNA-seq analysis. Our analysis revealed the developmental trajectory of the uDCs along with the distinct functional roles of each uDC subtype, including immune regulation, antigen presentation, and creating a conducive environment for embryo implantation. This study provides a comprehensive characterization of uDCs, serving as a foundational reference for future studies for better understanding of female reproductive disorders such as infertility and pregnancy complications.