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Series GSE128987 Query DataSets for GSE128987
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
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.
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.
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
Submission date Mar 28, 2019
Last update date Dec 09, 2021
Contact name Antoine-Emmanuel Saliba
Phone +49-931-31-81341
Organization name Helmholtz Institute for RNA-based Infection Research
Street address Josef-Schneider-Straße 2 / D15
City Würzburg
ZIP/Postal code 97080
Country Germany
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (5)
GSM3689561 G9
GSM3689562 G10
GSM3689563 G11
BioProject PRJNA529644
SRA SRP189742

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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
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Raw data are available in SRA
Processed data provided as supplementary file

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