Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia
| Autor: | Mandy Mangler, Naveen Kumar, Hilmar Berger, Stefanie Koster, Dajung Son, Marina Drabkina, Kirstin Hoffmann, Antoine-Emmanuel Saliba, Volker Brinkmann, Jörg Vogel, Hans-Joachim Mollenkopf, Hermann Herbst, Oliver Dietrich, Rajendra Kumar Gurumurthy, Cindrilla Chumduri, Thomas F. Meyer, Uwe Klemm, Panagiota Arampatzi |
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| Přispěvatelé: | HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell signaling
Stromal cell Transcription Genetic Uterine Cervical Neoplasms Cervical Metaplasia Cervix Uteri Stem cells Adenocarcinoma Biology Epithelium Article Stroma Metaplasia Developmental biology Biomarkers Tumor medicine Animals Homeostasis Humans Compartment (development) Cell Lineage Wnt Signaling Pathway Cancer Receptors Notch Wnt signaling pathway Cell Differentiation Cell Biology Cell biology ErbB Receptors Gene Expression Regulation Neoplastic Mice Inbred C57BL Organoids Cellular Microenvironment Carcinoma Squamous Cell Keratins Female Stromal Cells Stem cell medicine.symptom Cell signalling |
| Zdroj: | Nature cell biology England Nature Cell Biology |
| Popis: | 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. Chumduri, Gurumurthy et al. show that cervical squamous and columnar epithelia derive from two stem cell populations, regulated by opposing Wnt signals, and that a Wnt-repressive environment can induce metaplasia. |
| Databáze: | OpenAIRE |
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