Spatial Rewiring of Enterocyte Identity in Celiac Disease [snRNA-Seq]

In celiac disease (CeD), autoimmune destruction of enterocytes leads to villus blunting, but how this altered tissue morphology affects enterocyte states is unclear. Using spatial and single-cell transcriptomics, we show that in patients with CeD, enterocytes acquire a novel identity characterized by co-expression of multiple zonal programs.

This aberrant zonal co-expression results from reduced distances between BMP- and WNT-producing mesenchymal cells, leading to overlapping morphogen fields. In addition, we identify a subset of metaplastic cells that adopt gastric pit cell–like identities in discrete tissue patches. Our findings provide a detailed view of epithelial remodeling in CeD and establish a resource for understanding the cellular basis of malabsorption associated with villus blunting.