Digital Cell Atlas of Mouse Uterus: From Regenerative Phase to Maturational Phase

Abstract

Background: Endometria undergo repeated repair and regeneration during the menstrual cycle. Using gene expression to define the menstrual cycle has been seen in a couple of researches, which shares little consistency. The possible reason lies in the fact that the composition of each specimen is different. The objective of this study was to reconstruct an integrated cell atlas of mouse uterus from the regenerative to maturational endometrium at the single-cell level.Methods: We used published single-cell RNA sequencing data of mice uteri to build an integrated cell atlas, including epithelial cells, stromal cells, and immune cells. Principal components analysis, hierarchical clustering, and other data mining procedures were performed with R software. Functional enrichment analyses were performed to identify the potential biological roles of molecular changes in different mice estrus states.Results: Based on the expression level of proliferating cell nuclear antigen and gene ontology terms, we reconstructed the cell atlas and delineated in detail the transitions that happened during the estrus cycle. We also depicted the transition and transcription factors that shaped the differentiation of ESCs and the mononuclear phagocyte system. Besides, the amounts and functions of immune cells varied sharply in two periods. We also found clues about uterus tissue-resident macrophages and Pdgfrb+ Aldh1a2+ Cd34+ endometrial mesenchymal stem cells in vivo.Conclusions: The cell atlas of mouse uterus presented here would improve our understanding of the functional changes that occurred in the endometrium and helped us identify abnormalities that have not been apparent histologically.