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

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Abstract

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.

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Author notes

  1. Ahmad Salamian

    Present address: Current address: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Warszawa, Poland

  2. These two authors contributed equally to this work.

Authors and Affiliations

  1. Biology Department, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Marjan Taheri & Shiva Irani

  2. Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

    Ahmad Salamian, Kamran Ghaedi, Maryam Peymani, Tayebeh Izadi, Alireza Shoaraye Nejati, Atefeh Atefi, Marzieh Nematollahi, Fatemeh Ahmadi Ghahrizjani, Maryam Esmaeili, Abbas Kiani Esfahani & Mohammad Hossein Nasr-Esfahani

  3. Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran

    Kamran Ghaedi

  4. Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

    Hossein Baharvand

  5. Department of Developmental Biology, University of Science and Culture, ACECR, Tehran, Iran

    Hossein Baharvand

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  1. Marjan Taheri
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Correspondence to Kamran Ghaedi or Mohammad Hossein Nasr-Esfahani.

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Taheri, M., Salamian, A., Ghaedi, K. et al. A ground state of PPARγ activity and expression is required for appropriate neural differentiation of hESCs. Pharmacol. Rep 67, 1103–1114 (2015). https://doi.org/10.1016/j.pharep.2015.04.011

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  • DOI: https://doi.org/10.1016/j.pharep.2015.04.011

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