Fig. 2: Fetal FOXL1-positive telocyte progenitors partition into villus cluster and intervillus populations.
From: Villification of the intestinal epithelium is driven by Foxl1 through activation of PDGFRα and BMPs
A Foxl1-positive cells labeled by tdTomato expression reorganize during the epithelial transition, when the pseudostratified epithelium (E14.5) is converted to a simple cuboidal epithelium (E16.5). Epithelial cells are labeled with E-cadherin in green, Foxl1-positive cells by tdTomato in red. B Experimental outline for single cell RNAseq study. The proximal half of the E15.5 small intestine was used for the analysis. C UMAP plot of scRNAseq data identifies more than a dozen cell types. Foxl1-positive cells are labeled as telocyte progenitors 1 and 2 D UMAP plot showing that Foxl1 transcripts are confined to the telocyte progenitor clusters. E RNA velocity analysis suggests that telocyte progenitor 2 cells (yellow) give rise to both telocyte progenitor 1 cells as well as two Foxl1 negative mesenchymal cell populations. F UMAP plot of mRNA expression Pdgfra and several BMP genes in the two telocyte progenitor populations. G UMAP plot of mRNA abundance for Glp2r, encoding the receptor for the intestinotrophic hormone GLP-2. H Violin plot showing the enrichment of Glp2r transcripts in the telocyte progenitor 1 population. I RNAscope analysis of fetal mouse intestine from E15.5 fetuses localizes Glp2r transcripts (green) and Foxl1 mRNA (purple). J UMAP plot of mRNA abundance for Sall1, encoding the spalt like transcription factor 1, a zinc finger transcriptional repressor. K Violin plot showing the enrichment of Sall1 transcripts in the telocyte progenitor 1 population. L Immunofluorescence staining of anterior small intestine from E15.5 fetuses with antibodies specific to Sall1 (green) and Foxl1 (red) show localized expression in villus tip telocytes, as well as in a newly forming villus cluster. DAPI (blue) was used to visualize nuclei. M Model of relative positioning and prominent marker genes of telocyte progenitors 1 and 2 during intestinal villification. For imaging analyses (A, I, and L), 3–5 embryos per genotype at the indicated developmental stage were examined, and representative images are shown. Single-cell RNA sequencing was performed using small intestines from three embryos per genotype (E15.5), all collected from the same litter to ensure matched developmental stages and to minimize batch variability. Panel B Created in BioRender. Kaestner, K. (2026) https://BioRender.com/wnlyvi4Created in BioRender. Kaestner, K. (2026) https://BioRender.com/utcw1bv.
