GSE136653
Bmp2 -driven terminal differentiation of the stomach epithelium is induced by an autocrine Bmp2 positive feedback loop and inhibited by H. pylori via Interferon gamma signaling [RNA-seq]
We find that Bmp2 expression in the surface epithelium of the stomach provides a decisive, dominant fate-determining signal in the gland resulting in terminal differentiation. Terminal differentiation is induced by Bmp2 expression controlled by Bmp2 itself, creating an auto- and paracrine loop that maintains the cells in the differentiated state. Infection with H. pylori leads to a loss of stromal and epithelial Bmp2 expression resulting in gland hyperplasia and impaired differentiation. We demonstrate that Interferon gamma blocks endogenous Bmp2 expression and therefore Bmp2 signaling. Its effect on differentiated cells via Bmp2 inhibition maintains plasticity in this compartment, allowing for recruitment of differentiated cells to the stem cell pool, accounting for the rearrangement of stem cell compartment and increased plasticity in the epithelium in the context of epithelial damage in the gastrointestinal tract. Overall design: RNAseq of Myh11+ myofibroblasts from 3x uninfected and 3x H. pylori infected mice