How BMP signalling regulates stem cell self-renewal and/or differentiation

LGR5 (leucine-rich repeat containing G protein-coupled receptor 5) is a transmembrane protein expressed by intestinal stem cells that are responsible for maintaining intestinal homeostasis. BMP (bone morphogenetic protein) signalling plays a significant role in regulating stem cell self-renewal and/or differentiation in the intestinal niche. Experimental evidence has demonstrated that BMP stimulation of LGR5+ stem cells leads to the expression of a transcriptional repressor called Tcf-1 (T-cell factor 1). Tcf-1 is a negative regulator of stem cell self-renewal, acting in a competitive manner with the Wnt signalling pathway, which is known to regulate stem cell self-renewal. This evidence suggests that BMP stimulation of LGR5+ stem cells results in the repression of the Wnt pathway and promotes differentiation of the stem cells. In another study, it was shown that BMP signalling is required for the maintenance of the LGR5+ stem cell population by regulating the expression of the Notch receptor, which is another important regulator of stem cell self-renewal. Furthermore, it was demonstrated that BMP stimulates the expression of the Delta-like (DLL) ligand in the niche, which is required for the activation of the Notch signalling pathway. These data suggest that BMP signalling is important for the maintenance of the LGR5+ stem cell niche by regulating the expression of genes involved in both self-renewal and differentiation. Taken together, these studies suggest that BMP plays a key role in regulating the LGR5+ stem cell niche by controlling the expression of genes involved in both stem cell self-renewal and differentiation.