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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 26, 2020 |
| Title |
Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Balb/c mice were euthanized and the genital tract was extracted. Endocervix, ecto-endo junction and ectocervix were seperated from healthy mice. In addition, a metaplasia sample was processed twice, as a technical replicate, after extraction from an in vivo mouse model of cervical metaplasia.
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| Contributor(s) |
Chumduri C, Gurumurthy RK, Berger H, Dietrich O, Kumar N, Koster S, Brinkmann V, Hoffmann K, Drabkina M, Arampatzi P, Son D, Klemm U, Mollenkopf HJ, Herbst H, Mangler M, Vogel J, Saliba AE, Meyer TF |
| Citation(s) |
33462395, 34841281 |
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| Submission date |
Mar 28, 2019 |
| Last update date |
Dec 09, 2021 |
| Contact name |
Antoine-Emmanuel Saliba |
| E-mail(s) |
emmanuel.saliba@helmholtz-hzi.de
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| Phone |
+49-931-31-81341
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| Organization name |
Helmholtz Institute for RNA-based Infection Research
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| Street address |
Josef-Schneider-Straße 2 / D15
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| City |
Würzburg |
| ZIP/Postal code |
97080 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA529644 |
| SRA |
SRP189742 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128987_RAW.tar |
1.1 Gb |
(http)(custom) |
TAR (of CSV, H5, TAR) |
| GSE128987_README.txt |
318 b |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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