Back to Search
Start Over
Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia
- Source :
- Nature cell biology, England, Nature Cell Biology
- Publication Year :
- 2021
- Publisher :
- Nature research, 2021.
-
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.<br />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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Nature cell biology, England, Nature Cell Biology
- Accession number :
- edsair.doi.dedup.....9e3efb0115410b2fa78b455f997dfb0d