Figure 7.

Proposed model of NPR-A signaling-mediated maintenance of ES cell self-renewal and pluripotency. Activation of NPR-A by ANP stimulates the cGMP/PKG signaling pathway, leading to increased expressions of Oct4 and Nanog, and reduced expression of p21, which in turn suppresses ES cell differentiation and maintains ES cell pluripotency. In another pathway, binding of ANP to NPR-A activates the phosphoinositide 3-kinase (PI3K) signaling pathway, which enhances G1-to-S progression through induction of cyclin D1, and maintains pluripotency by activation of Nanog expression