The female reproductive system, the uterus, fallopian tubes and the ovaries, is a complex interrelated set of organs that is physiologically dynamic and not only important for fertility but critically interrelated with general health. Single cell studies of the human female reproductive system and related tissues have been previously studied, but, as of yet, a comprehensive program, aligned with the goals of the HuBMAP, to define a molecular map of the entire system, integrating multi-modal assays, spatial diversity, and individual variations has not been established. The Penn Department of Obstetrics and Gynecology performs approximately 3,500 surgical procedures annually, of which many procedures allow sampling of multiple organs and locations from the same subject under normal conditions. Here, we propose to leverage the sampling opportunities afforded by the Penn ObGyn group and the single cell biology expertise of Penn investigators to establish a Penn Center for Multi-scale Molecular Map of the Female Reproductive System. We will obtain a comprehensive molecular characterization of the female reproductive system using six different molecular assays for at least ~700 tissue samples in anatomically indexed samples, creating a key resource for both basic science and women?s health. The molecular assays include single cell RNAseq, clampFISH spatial transcriptomics, simultaneous single cell open chromatin and RNA assays, and spatial open chromatin assay, among others. We will also generate a 3D anatomical model to provide spatial coordinate for our molecular characterization. All assay data will be registered to our 3D anatomical map that will be integrated with the HIVE Common Coordinate Framework. All metadata from subject records, clinical procedures, molecular procedures, and informatics pipelines will be collected, curated, and deposited as structured data. All data, including an extensive set of metadata, will be made available as a public resource. The completion of this resource will impact reproductive medicine for women?s health and also inform basic biology of human cell communities.
We propose to create a comprehensive resource for women?s health by studying the molecular characteristics of individual cells in the female reproductive system. Our cellular atlas will uncover the complex interactions of cells that determine reproductive health and help with therapeutic strategies.
