Dual effects of peroxisome proliferator-activated receptor γ on embryonic stem cell self-renewal in presence and absence of leukemia inhibitory factor

Abstract

The aim of this study was to evaluate the influence of peroxisome proliferator-activated receptor γ (PPARγ) on self-renewal of mouse embryonic stem cells (mESCs) in the presence and absence of leukemia inhibitory factor (LIF). We demonstrated that in the presence of LIF, the activation of PPARγ by Rosiglitazone led to an increased proliferation of mESCs whereas PPARγ antagonist (GW9662) reversed this effect. Additionally, upon PPARγ activation, LIF increased PPARγ expression and resulted in the degradation of suppressor of cytokine signaling 3 (SOCS3), an important negative regulator of LIF/signal transducers and activators of transcription 3 (STAT3)-pathway. In the absence of LIF, Rosiglitazone decreased proliferation of mESCs. In this state, our results showed that extracellular signal-regulated kinase (ERK) proteins were activated and resulted in the suppression of Nanog expression, an important pluripotency determinant, whereas it did not affect Oct4 expression. These results suggest that the pivotal role of PPARγ on mESC self-renewal depends on the presence and absence of LIF.