Postdoctoral Researcher Karolinska Institutet, Sweden
Abstract: The basal cells of the esophageal epithelium have traditionally been considered a homogeneous population. However, work from our group suggest that organoid forming efficiency as well as ability to generate basal clones in vivo differ along the proximal-distal esophageal axis. Combining single-cell sequencing with spatial transcriptomics, we identified location-specific differences in the transcriptome of proximal and distal basal cells. In addition, the distal esophageal epithelium displayed circumferential transcriptional heterogeneity, correlating to the folding of the esophageal tube. To validate these findings, we employ two Cre-dependent reporter mouse lines that selectively mark either folded or extended distal epithelial regions. Genetic labeling and tracing of basal cells in folds and extensions will reveal differences in progenitor cell behavior in vivo. Additionally, our spatial transciptomics characterization allowed us to map back specific subpopulation of fibroblasts to esophageal cross sections, identifying region-specific fibroblast-epithelial basal cell interactions. Bioinformatic analysis revealed local differences in predicted fibroblast-basal cell signaling, with Wnt and TGF-β pathway activity enriched in extended regions. These findings provide new insights into the spatial regulation of progenitor cell behavior in the esophageal epithelium.
