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

Phoebe M Kirkwood, Douglas A Gibson, Isaac Shaw, Ross Dobie, Olympia Kelepouri, Neil C Henderson, Philippa T. K. Saunders
eLife · 2022 · vol. 11 · doi:10.7554/elife.77663 · PMID:36524724 · W4311672715
article OA: gold CC0 ⤵ 13 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study used single-cell RNA sequencing and lineage tracing in mice to demonstrate that endometrial stromal fibroblasts can transform into epithelial cells and contribute to tissue repair after menstruation.

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Abstract

The human endometrium experiences repetitive cycles of tissue wounding characterised by piecemeal shedding of the surface epithelium and rapid restoration of tissue homeostasis. In this study, we used a mouse model of endometrial repair and three transgenic lines of mice to investigate whether epithelial cells that become incorporated into the newly formed luminal epithelium have their origins in one or more of the mesenchymal cell types present in the stromal compartment of the endometrium. Using scRNAseq, we identified a novel population of PDGFRb + mesenchymal stromal cells that developed a unique transcriptomic signature in response to endometrial breakdown/repair. These cells expressed genes usually considered specific to epithelial cells and in silico trajectory analysis suggested they were stromal fibroblasts in transition to becoming epithelial cells. To confirm our hypothesis we used a lineage tracing strategy to compare the fate of stromal fibroblasts (PDGFRa+) and stromal perivascular cells (NG2/CSPG4+). We demonstrated that stromal fibroblasts can undergo a mesenchyme to epithelial transformation and become incorporated into the re-epithelialised luminal surface of the repaired tissue. This study is the first to discover a novel population of wound-responsive, plastic endometrial stromal fibroblasts that contribute to the rapid restoration of an intact luminal epithelium during endometrial repair. These findings form a platform for comparisons both to endometrial pathologies which involve a fibrotic response (Asherman's syndrome, endometriosis) as well as other mucosal tissues which have a variable response to wounding.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Mesenchymal Stem Cells Mesenchymal Stem Cells Mesenchymal Stem Cells Mesenchymal Stem Cells Mesenchymal Stem Cells Mesenchymal Stem Cells Animals Animals Animals Animals Animals Endometrium Endometrium Endometrium Endometrium

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