or less The LGR5+ Stem Cell Niche Uses BMP Signaling to Regulate Its Self-Renewal and/or Differentiation

LGR5+ Stem Cells (LSCs) are a type of adult stem cell that are found in the intestinal crypt niche and are responsible for the continuous intestinal epithelial cell (IEC) renewal throughout adulthood. BMP signalling is known to play a role in the regulation of the self-renewal and differentiation of LSCs. Studies have employed in vitro and in vivo approaches to further understand this role of BMPs in LSCs and how it can be modulated to regulate their behaviour. In vitro studies have mainly focused on the ability of BMPs to modulate the expression of Wnt pathway genes in LSCs. Wnt pathway genes are important for LSCs self-renewal and differentiation, and the in vitro studies have shown that the glycogen synthase kinase 3 beta (GSK3ß) inhibitor, SB-216763, can increase BMP signalling in LSCs and decrease the expression of Wnt pathway genes. SB-216763 has been shown to reduce the Wnt-dependent maintenance of LSCs and increase their differentiation. This indicates a possible role of BMPs in regulating the behaviour of LSCs in vitro. In vivo studies have focused on using transgenic mice to investigate the role of BMP signalling in LSCs. Mutations in genes that are part of the BMP signalling cascade have been used to assess their effects on LSCs in vivo. One gene, Smad4, has been found to be important for LSCs as mice with Smad4 mutated were found to have a smaller proportion of proliferative LSCs and a higher proportion of differentiated LSCs. This has been shown to be due to the aberrant activation of BMP signalling in mice with Smad4 mutated. Other studies have used genetic engineering to perturb BMP signalling in vivo. In one study, overexpression of the BMP antagonist, Noggin, was found to decrease the number of active LSCs and increase their cell cycling time. In another study, a dominant-negative BMP receptor was expressed in LSCs of mice, which resulted in increased proliferation and decreased differentiation of LSCs. Overall, these studies have highlighted a role of BMP signalling in regulating the behaviour of LSCs. BMP signalling can either promote or inhibit the self-renewal and differentiation of LSCs