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Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia.
Chumduri, Cindrilla Gurumurthy, Rajendra Kumar Berger, Hilmar Dietrich, Oliver Kumar, Naveen Koster, Stefanie Brinkmann, Volker Hoffmann, Kirstin Drabkina, Marina Arampatzi, Panagiota
Chumduri, Cindrilla
Gurumurthy, Rajendra Kumar
Berger, Hilmar
Dietrich, Oliver
Kumar, Naveen
Koster, Stefanie
Brinkmann, Volker
Hoffmann, Kirstin
Drabkina, Marina
Arampatzi, Panagiota
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2021-01-18
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Abstract
The transition zones of the squamous and columnar epithelia constitute hotspots for the emergence of cancer, often preceded by metaplasia, in which one epithelial type is replaced by another. 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.
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Nat Cell Biol. 2021 Feb;23(2):184-197. doi: 10.1038/s41556-020-00619-0. Epub 2021 Jan 18.
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en
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1476-4679
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Attribution 4.0 International