A ground state of PPAR gamma activity and expression is required for appropriate neural differentiation of hESCs

作者：Taheri Marjan; Salamian Ahmad; Ghaedi Kamran^*; Peymani Maryam; Izadi Tayebeh; Nejati Alireza Shoaraye; Atefi Atefeh; Nematollahi Marzieh; Ghahrizjani Fatemeh Ahmadi; Esmaeili Maryam; Esfahani Abbas Kiani; Irani Shiva; Baharvand Hossein; Nasr Esfahani Mohammad Hossein

来源：Pharmacological Reports, 2015, 67(6): 1103-1114.

DOI：10.1016/j.pharep.2015.04.011

• 15d-PGJ2
• Human embryonic stem cells
• Neural differentiation
• Pioglitazone
• PPAR gamma

Background: Several evidences indicate stimulation of peroxisome proliferator activated receptor gamma (PPARg), promotes neuronal differentiation. This study was conducted to testify the prominence of PPAR gamma during neural differentiation of human embryonic stem cells (hESCs).
Methods: PPAR gamma expression level was assessed during neural differentiation of hESCs. Meanwhile, the level of endogenous miRNAs, which could be engaged in regulation of PPAR gamma expression, was measured. Next, natural and synthetic components of PPAR gamma agonists and antagonist were implemented on neural progenitor formation during neural differentiation of hESCs.
Results: Data showed an increasing wave of PPAR gamma expression level when human neural progenitors (NPs) were formed upon retinoic acid treatment. Interestingly, there was no significant difference in the amount of PPAR gamma proteins during the differentiation of hESCs that is inconsistent with what we observed for RNA level. Our results indicated that miRNAs are not involved in the regulation of PPAR gamma expression, while proteasome-mediated degradation may to some degree be involved in this process. Among numerous treatments, PPAR gamma inactivation during NPs formation significantly decreased expression of NP markers.
Conclusions: We conclude that a ground state of PPAR gamma activity is required for NP formation of hESCs during early neural differentiation. However, high expression and activity of PPAR gamma could not enhance the required neural differentiation, whereas the PPAR gamma inactivation could negatively influence NP formation from hESCs by antagonist.

• 出版日期2015