Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia
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ABSTRACT:
PROVIDER: PRJNA529644 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR8799038.fastq.gz | Fastqsanger.gz |
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Project description:The transition zones (TZs) of the squamous and columnar epithelium constitute hotspots for the emergence of cancers, often preceded by metaplasia, where one epithelial type is replaced by cells of another type. Yet, it remains uncertain how the spatial organization of the epithelia is maintained and how the TZ niche is remodeled during metaplasia. Here, we used single-cell RNA-sequencing to characterize subpopulations of the epithelium as well as the underlying stromal compartment of endo and ectocervix, encompassing the TZ. Mouse lineage tracing, organoid culture and smRNA-ISH revealed that the two epithelia derive from two separate cervix-resident lineage-specific stem cell populations that are regulated by opposing WNT signals from the stroma. Using a mouse model of cervical metaplasia, we further show that the endocervical stroma undergoes remodeling and increased expression of WNT signaling inhibitor Dickkopf-2 (DKK2), promoting the outgrowth of ectocervical stem cells. Thus, homeostasis at the TZ results from divergent stromal signals, driving the differential proliferation of resident epithelial lineages.
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Project description: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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