Journal
JOURNAL OF PATHOLOGY
Volume 251, Issue 4, Pages 440-451Publisher
WILEY
DOI: 10.1002/path.5478
Keywords
3D reconstruction; lineage tracing; endometrium; regeneration; stem cells
Funding
- Wellbeing of Women project [RTF510, RG2137]
- Cancer Research UK [A14895]
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Regular menstrual shedding and repair of the endometrial functionalis is unique to humans and higher-order primates. The current consensus postulates endometrial glands to have a single-tubular architecture, where multi-potential stem cells reside in the blind-ending glandular-bases. Utilising fixed samples from patients, we have studied the three-dimensional (3D) micro-architecture of the human endometrium. We demonstrate that some non-branching, single, vertical functionalis glands originate from a complex horizontally interconnecting network of basalis glands. The existence of a multipotent endometrial epithelial stem cell capable of regenerating the entire complement of glandular lineages was demonstrated byin vivolineage tracing, using naturally occurring somatic mitochondrial DNA mutations as clonal markers. Vertical tracking of mutated clones showed that at least one stem-cell population resides in the basalis glands. These novel findings provide insight into the efficient and scar-less regenerative potential of the human endometrium. (c) 2020 The Authors.The Journal of Pathologypublished by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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