Single cell insights into epithelial morphogenesis in the neonatal mouse uterus

The uterus is an essential organ for reproduction in mammals, however the cellular and molecular mechanisms that direct its development remain insufficiently understood. To fill this knowledge gap, the epithelium of the neonatal mouse uterus was isolated and subjected to single cell transcriptome (scRNA-seq) analysis. Substantial differences in transcriptional profiles and cell types were evident as the epithelium developed from postnatal days 1 to 15. Both the undifferentiated epithelium and determined luminal epithelium were heterogeneous and contained several different cell clusters. Novel glandular epithelial-specific genes (Gas6 and Cited4) were validated by in situ hybridization during uterine development. Trajectory analyses provided a framework for understanding epithelium maturation and differentiation of the glandular epithelium. A candidate set of transcription factors and gene regulatory networks were identified that regulate epithelium lineage specification and morphogenesis. This atlas provides foundational insights important for future mechanistic studies focused on uterine epithelium morphogenesis during the critical window of postnatal development. Overall design: Nuclei were isolated and libraries prepared following the 10X Genomics platform protocols