Author response: Single-cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation

The paper integrates single-cell RNA sequencing with lineage tracing and trajectory analyses to test whether mesenchyme-to-epithelial transformation (MET) contributes to repair of the mouse endometrium at menstruation, focusing on specific stromal (fibroblast) subpopulations and an epithelial-associated trajectory. Key findings include identification of fibroblast subclusters that transcriptionally relate to epithelial lineage states and trajectory/velocity results supporting an origin of epithelial-like cells from a particular fibroblast subpopulation, with additional GSEA and batch-corrected dataset integration used to support EMT/MET-related gene programs and fibroblast–epithelial links. A major caveat acknowledged in peer review response is that some interpretations of apoptotic/dying cells (cluster F5) were based on in silico metrics rather than direct validation, and the reviewers also noted limitations in human scRNA-seq depth and sampling at menstrual stages. Relevance to endometriosis: the study is centrally about endometrial repair during menstruation, which is mechanistically adjacent to menstrual tissue/immune interactions implicated in endometriosis and is included in the corpus via its explicit focus on the endometrium at menstruation.

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