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The current consensus postulates endometrial glands to have a single\u2010tubular architecture, where multi\u2010potential stem cells reside in the blind\u2010ending glandular\u2010bases. Utilising fixed samples from patients, we have studied the three\u2010dimensional (3D) micro\u2010architecture of the human endometrium. We demonstrate that some non\u2010branching, 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 by <jats:italic>in vivo<\/jats:italic> lineage tracing, using naturally occurring somatic mitochondrial DNA mutations as clonal markers. Vertical tracking of mutated clones showed that at least one stem\u2010cell population resides in the basalis glands. These novel findings provide insight into the efficient and scar\u2010less regenerative potential of the human endometrium. \u00a9 2020 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5478","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T03:56:53Z","timestamp":1590983813000},"page":"440-451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Histological <scp>3D<\/scp> reconstruction and <i>in vivo<\/i> lineage tracing of the human endometrium"],"prefix":"10.1002","volume":"251","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3633-1592","authenticated-orcid":false,"given":"Nicola","family":"Tempest","sequence":"first","affiliation":[{"name":"Liverpool Women's Hospital NHS Foundation Trust, member of the Liverpool Health 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