Spatial transcriptomics reveals coordinated architecture of uterine lining regeneration during menstrual cycle
Researchers used high-resolution spatial transcriptomics to map gene expression across the full thickness of the human endometrium, profiling over ten million cells from biopsies, hysterectomy samples, and menstrual fluid. The study found that endometrial breakdown and regeneration occur simultaneously rather than sequentially, organized across distinct tissue compartments, and identified a previously undescribed quiescent progenitor-like epithelial cell population in the basalis layer supported by specialized SFRP5+ fibroblasts. These findings provide a molecular framework that could improve understanding of menstrual disorders, implantation failure, and impaired tissue repair.
A preprint study posted to bioRxiv presents a comprehensive spatial transcriptomic atlas of the human endometrium, mapping gene expression gradients from the myometrial-endometrial boundary to the luminal surface at high resolution. The researchers integrated spatial transcriptomics with single-cell transcriptomics, profiling more than ten million cells and deliberately enriching for the menstrual and proliferative phases, which have been underrepresented in prior research. A central finding challenges the conventional view that tissue shedding and regeneration are temporally separated: the data show these processes occur concurrently, organized across anatomically distinct compartments. The study resolves the basalis epithelial niche at molecular resolution for the first time, identifying a discrete, predominantly quiescent progenitor-like epithelial subset alongside specialized SFRP5+ fibroblasts, both characterized by WNT pathway inhibition, as well as lymphoid aggregates forming a multi-component niche architecture. This regenerative niche structure was found to persist after menopause, suggesting it functions as a long-lived reservoir rather than a cycle-dependent structure. Continuous transcriptional gradients linking progenitor identity, niche signaling, and tissue remodeling were identified as a central organizing principle of endometrial renewal. The authors propose that these findings have clinical relevance for conditions including abnormal uterine bleeding, endometriosis, implantation failure, and scarring disorders.
What's missing
As a preprint, this study has not yet undergone peer review, and its findings should be interpreted with that caveat. The study does not report functional validation experiments confirming that the identified quiescent progenitor-like epithelial subset is causally responsible for regeneration. The study also does not address whether the identified niche architecture differs in individuals with menstrual or implantation disorders, which is a key translational question raised by the authors.
What different sources said
- bioRxivCenter
Full-thickness spatial transcriptomics of the human uterus reveals basalis niche architecture and regeneration gradients during menstrual breakdown
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