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, molecular characteristics, and specific roles during the pre- and post-implantation periods in the human endometrium remain largely unknown. The complexity of the endometrial environment makes defining the contributions of uDCs subtypes challenging. We hypothesize that distinct uDC subsets carry out specialized functions, and that resident progenitor DCs generate these subtypes. Employing single-cell RNA sequencing on uterine tissues collected across different menstrual phases and during early pregnancy, we identify several uDCs subtypes, including resident progenitor DCs. CITE-seq was performed on endometrial single-cell suspensions to link surface protein expression with key genes identified by the RNAseq 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 female reproductive disorders such as infertility and pregnancy complications. Endometrial biopsies were collected from healthy patients across 10 distinct stages of the menstrual cycle, determined using a precise cycle tracking method. Single-cell suspensions were prepared, and cells were extracted using fluorescence-activated cell sorting (FACS) to enrich for specific populations. The extracted cells were then sequenced using the MARS-seq (Massively Parallel RNA Single-Cell Sequencing) platform, enabling high-resolution analysis of gene expression profiles across the different phases of the menstrual cycle. *************************************************************** raw data not provided ***************************************************************