Single-cell sequencing reveals a regulatory role of WT1 in mast cell proliferation in endometrial polyps.

Endometrial polyps are the predominant structural anomalies of the endometrial mucosa observed in unexplained infertility cases, potentially compromising endometrial receptivity and suggesting shared etiological characteristics. However, their comprehensive cell atlas and immune landscape remain inadequately defined. In this study, we employed single-cell RNA sequencing and bulk RNA-seq to systematically analyze ectopic endometrial polyps (EPs) alongside adjacent eutopic endometrial tissues (EUs). This enabled us to delineate alterations in cell composition and transcriptional dynamics across diverse cell types associated with endometrial polyps. Notably, we observed an increase and activation of mast cells, with significant transcriptional profile variations. Through transcription regulatory network analysis, WT1 was identified as a pivotal transcriptional regulator mediating mast cell proliferation in EPs, concomitant with the dysregulation of WT1 target genes involved in cell growth. These findings provide novel insights into the cellular heterogeneity and molecular mechanisms of endometrial polyps at single-cell resolution, presenting potential therapeutic targets for clinical intervention.