How the Notch Signaling Pathway and Mediator Work Together to Regulate hASC Self-Renewal

Obesity is a serious medical condition resulting from excess body fat that triggers changes in both quantity and quality of various cells that reside in adipose tissue, including adipose stem cells. Adipose derived stem cells are multipotent, self-renewing cells that have the ability to differentiate. This process can be controlled by environmental stimuli, transcription factors, and signal cascades that lead to gene transcription and protein expression specific to the cell’s fate. The Mediator complex and the Notch signaling pathway are two complexes that allow this to occur. There is still much unknown about the Mediator complex, the Notch signaling pathways, and their interaction, especially during adipogenesis. Here we describe the expression profile and activity of MED12, Notch1, Notch3, Jagged1, and Jagged2 in self-renewing human adipose stem cells and determine the impact each gene has on expression and activity in self-renewing hASC’s. We observed a MED12 knockdown leads to decreased expression and activation of Notch3; MED12 may be required to regulate the transcript and expression of Notch3. Notch3 knockdown leads to decrease MED12 transcript and protein; Notch3 may be required to maintain appropriate levels of MED12 expression. Jagged1 knockdown leads to a decrease in MED12 transcript, but has no discernible effects on protein expression. More research is needed to investigate the relationship between Jagged1 and Notch3