Single-cell omics technologies - Fundamentals on how to create single-cell looking glasses for reproductive health

Over the last decade, in line with the goals of precision medicine to offer individualized patient care, various single-cell technologies measuring gene and proteomic expression in various tissues have rapidly advanced to study health and disease at the single cell level. Precisely understanding cell composition, position within tissues, signaling pathways, and communication can reveal insights into disease mechanisms and systemic changes during development, pregnancy, and gynecologic disorders across the lifespan. Single-cell technologies dissect the complex cellular compositions of reproductive tract tissues, providing insights into mechanisms behind reproductive tract dysfunction which impact wellness and quality of life. These technologies aim to understand basic tissue and organ functions and, clinically, to develop novel diagnostics, early disease biomarkers, and cell-targeted therapies for currently suboptimally-treated disorders. Increasingly, they are applied to pregnancy and pregnancy disorders, gynecologic malignancies, and uterine and ovarian physiology and aging, which are discussed in more detail in manuscripts in this special issue of AJOG. Here, we review recent applications of single-cell technologies to the study of gynecologic disorders and systemic biological adaptations during fetal development, pregnancy, and across a woman's lifespan. We discuss sequencing- and proteomic-based singlecell methods, as well as spatial transcriptomics and high-dimensional proteomic imaging, describing each technology's mechanism, workflow, quality control, and highlighting specific benefits, drawbacks, and utility in the context of reproductive medicine. We consider analytical methods for the high-dimensional single-cell data generated, highlighting statistical constraints and recent computational techniques for downstream clinical translation. Overall, current and evolving single-cell "looking glasses", or perspectives, have the potential to transform fundamental understanding of women's health and reproductive disorders and alter the trajectory of clinical practice and patient outcomes in the future.