Fig. 6: Endocervical stroma undergoes extensive remodelling during metaplasia.
From: Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia
a–e, Combined scRNA-seq analysis of datasets derived from healthy mouse ectocervix, endocervix, transition zone and endocervix tissues with squamous metaplasia induced by vitamin A-deficient diet. UMAP of stromal subclusters coloured by sampled tissue (a) or cluster annotation (b). c, Sankey diagram showing the contribution of stromal cells from each tissue type to the clusters shown in b. Colours and labels for sampled tissue as in a (left) and subclusters as in b (right). d, Heat map of the top 5 genes expressed in each stromal subcluster shown in b. Colour bar denotes fold change from mean gene expression across all samples. e, Normalized expression values of Dkk2 on the UMAP. f, Tissue sections from the genital system of a mouse fed with a vitamin A-deficient diet for 15 weeks; labelling with antibodies against KRT7 and KRT5. Middle and bottom: magnified view of boxed regions, showing an outgrowth of subcolumnar KRT5+ stem cells that gave rise to a squamous metaplastic epithelium in the endocervix. Boxed areas labelled as I and II are magnified at the bottom. g,h, Confocal images showing KRT17, p63 and KRT5 in human ectocervical stratified epithelial tissue (g) and subcolumnar cells in endocervix (h); RC indicates reserve cells, nuclei in blue. i–l, Confocal images of cells positive for KRT8, p63, KRT5 or KRT17 in mouse ectocervical stratified epithelium (i,j), mouse endocervical tissue (k,l) and mouse endocervix with squamous metaplasia (m,n); nuclei in blue. o, smRNA-ISH of tissue from a mouse fed with a vitamin A-deficient diet. The expression of Dkk2 is enhanced in the endocervical stroma. Boxed areas labelled I and II are magnified (middle and bottom). p,q, Lineage tracing in Krt8-CreERT2;Rosa26-tdTomato (p) and Krt5-CreERT2;Rosa26-tdTomato (q) mice fed with a vitamin A-deficient diet revealed that squamous metaplasia arising in the endocervix is negative for Krt8-tdTomato (p) and positive for Krt5-tdTomato (q) lineage markers. Data shown in f–q are representative of biologically independent experiments from three mice or human samples. Tiled images shown in f,o–q were acquired with an AxioScan imager.
