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It remains unclear how the epithelial spatial organization is maintained and how the transition zone niche is remodelled during metaplasia. Here we used single-cell RNA sequencing to characterize epithelial subpopulations and the underlying stromal compartment of endo- and ectocervix, encompassing the transition zone. Mouse lineage tracing, organoid culture and single-molecule RNA in situ hybridizations revealed that the two epithelia derive from separate cervix-resident lineage-specific stem cell populations regulated by opposing Wnt signals from the stroma. Using a mouse model of cervical metaplasia, we further show that the endocervical stroma undergoes remodelling and increases expression of the Wnt inhibitor Dickkopf-2 (DKK2), promoting the outgrowth of ectocervical stem cells. Our data indicate that homeostasis at the transition zone results from divergent stromal signals, driving the differential proliferation of resident epithelial lineages.<\/jats:p>","DOI":"10.1038\/s41556-020-00619-0","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T12:04:35Z","timestamp":1610971475000},"page":"184-197","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":129,"title":["Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia"],"prefix":"10.1038","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3290-5966","authenticated-orcid":false,"given":"Cindrilla","family":"Chumduri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6479-8080","authenticated-orcid":false,"given":"Rajendra Kumar","family":"Gurumurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6304-4946","authenticated-orcid":false,"given":"Hilmar","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4776-8960","authenticated-orcid":false,"given":"Oliver","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2026-0446","authenticated-orcid":false,"given":"Naveen","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8449-9985","authenticated-orcid":false,"given":"Stefanie","family":"Koster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4735-3682","authenticated-orcid":false,"given":"Volker","family":"Brinkmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstin","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Drabkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7925-8984","authenticated-orcid":false,"given":"Panagiota","family":"Arampatzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1432-6103","authenticated-orcid":false,"given":"Dajung","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Klemm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1167-4783","authenticated-orcid":false,"given":"Hans-Joachim","family":"Mollenkopf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Herbst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Mangler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-1404","authenticated-orcid":false,"given":"J\u00f6rg","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8539-2784","authenticated-orcid":false,"given":"Antoine-Emmanuel","family":"Saliba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6120-8679","authenticated-orcid":false,"given":"Thomas F.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"619_CR1","doi-asserted-by":"publisher","first-page":"e1007384","DOI":"10.1371\/journal.ppat.1007384","volume":"14","author":"TA Ajayi","year":"2018","unstructured":"Ajayi, T. 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