Gastric Myofibroblasts Control Chief Cell differentiation, and their recovery from SPEM

Chief cells expressing Wnt/R-spondin target genes are located in the stomach corpus gland base. These cells can act as reserve stem cells and their transdifferentiation is a hallmark of spasmolytic polypeptide expressing metaplasia (SPEM). Mechanisms that control their differentiation, transdifferentiation and re-differenitiation are not fully understood. We investigated the function of R-spondin 3, a Wnt signaling activator and Lgr5 ligand, by using conditional mouse models that enable manipulation of R-spondin 3 gene expression in gastric myofibroblasts.The effect and the physiological function of R-spondin 3 was analyzed in the corpus and colon with R-spondin 3 gene knock-out mice in Myh11+ myofibroblasts (Myh11-CreERT2; Rspo3fl/fl (RSPO3 KO) or R-spondin 3 gene knock-in overexpressiong myofibroblasts ( Myh11-CreERT2/Rosa26Sor6(CAG–Rspo3) ( RSPO3 KI)). Microarray experiments were performed as dual-color hybridizations on Agilent whole mouse catalog 4x44K (Agilent-014868) and 8x60K (Agilent-074809) arrays. To compensate for dye-specific effects, a dye-reversal color-swap was applied.