Transcriptional Profiling of <scp>SSEA</scp> ‐1 ⁺ Endometrial Epithelial Progenitor Cells Highlights Their Role in Endometrial Regeneration, Remodeling, and Homeostasis

Stage-specific embryonic antigen-1 (SSEA-1)⁺ endometrial epithelial cells (EECs) assume the postulated stem/progenitor cell niche within the human endometrium. Previous studies have demonstrated that isolated SSEA-1⁺ cells have a higher capacity to generate organoids in a three-dimensional matrix, a lower steroid hormone receptor expression, and higher telomerase activity with longer telomere lengths. Here, we present the transcriptomic profile of isolated SSEA-1⁺ EECs from eight endometrial biopsies compared to SSEA-1^- EECs. Transcriptome and pathway analysis indicate that SSEA-1⁺ EECs play an important role in endometrial regeneration, remodeling and neovascularization as expected from a basal progenitor population. We show that SSEA-1⁺ EECs play a role in endometrial tissue homeostasis and tumor suppression, and bioinformatically identify potential upstream regulators such as SPDEF and TGFB1, which may be involved in these mechanisms. In vitro EEC organoid models also demonstrate SSEA-1⁺ EECs to exhibit estrogen responsive proliferation evidenced by stronger immunostaining for progesterone receptor and Ki-67. Our data further suggest a more quiescent, less hormone responsive phenotype for SSEA-1⁺ EECs that co-localize to SOX9⁺ EECs within in silico analysis, thus validating previous studies.