Molecular signature of human endometrial stem/progenitor cells at the single cell level

Human endometrium sheds and regenerates each month during the menstrual cycle. N-cadherin+ (CDH2) glandular epithelial progenitors and SUSD2+ MSC and their niches have been identified but their signaling interactions remain unknown. SSEA1+ epithelial cells resurface the endometrium generating a new luminal epithelium each cycle. Based on these markers, we characterised the gene expression of human endometrial stem/progenitor cell-enriched populations derived from FACSorted hysterectomy endometrium by scRNAseq. Two of 10 epithelial clusters contained CDH2+SOX9+ cells with high TRH and IHH expression. N-cadherin and IHH, and SSEA1 and Hedgehog coreceptor BOC immunocolocalised in the basal layer of endometrial glands from which the new functional layer glands regenerate each menstrual cycle. Two of six mesenchymal clusters contained SUSD2+ MSC, one with high MUSTN1 expression. Epithelial progenitors and endometrial MSC transitioned to their respective progeny. We provide new insights into human endometrial stem/progenitor cell signaling pathways and niche interactions regulating their function.