A ground state of PPARγ activity and expression is required for appropriate neural differentiation of hESCs.
BACKGROUND
Several evidences indicate stimulation of peroxisome proliferator activated receptor γ (PPARg), promotes neuronal differentiation. This study was conducted to testify the prominence of PPARγ during neural differentiation of human embryonic stem cells (hESCs).


METHODS
PPARγ expression level was assessed during neural differentiation of hESCs. Meanwhile, the level of endogenous miRNAs, which could be engaged in regulation of PPARγ expression, was measured. Next, natural and synthetic components of PPARγ agonists and antagonist were implemented on neural progenitor formation during neural differentiation of hESCs.


RESULTS
Data showed an increasing wave of PPARγ expression level when human neural progenitors (NPs) were formed upon retinoic acid treatment. Interestingly, there was no significant difference in the amount of PPARγ 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 PPARγ expression, while proteasome-mediated degradation may to some degree be involved in this process. Among numerous treatments, PPARγ inactivation during NPs formation significantly decreased expression of NP markers.


CONCLUSIONS
We conclude that a ground state of PPARγ activity is required for NP formation of hESCs during early neural differentiation. However, high expression and activity of PPARγ could not enhance the required neural differentiation, whereas the PPARγ inactivation could negatively influence NP formation from hESCs by antagonist.
Biology Department, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Marjan
M
Taheri
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Ahmad
A
Salamian
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran; Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran. Electronic address: kamranghaedi@royaninstitute.org.
Kamran
K
Ghaedi
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Maryam
M
Peymani
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Tayebeh
T
Izadi
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Alireza Shoaraye
AS
Nejati
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Atefeh
A
Atefi
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Marzieh
M
Nematollahi
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Fatemeh
F
Ahmadi Ghahrizjani
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Maryam
M
Esmaeili
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Abbas
A
Kiani Esfahani
Biology Department, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Shiva
S
Irani
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran.
Hossein
H
Baharvand
Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address: mh_nasr@royaninstitute.org.
Mohammad Hossein
MH
Nasr-Esfahani
D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D035683:MicroRNAs / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology
D007976:Leupeptins; D035683:MicroRNAs; D047495:PPAR gamma; D014212:Tretinoin; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
15d-PGJ2; Human embryonic stem cells; Neural differentiation; PPARγ; Pioglitazone