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PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes.
PLoS One. 2012; 7(11):e50500.Plos

Abstract

Neural stem cells (NSCs) are a small population of resident cells that can grow, migrate and differentiate into neuro-glial cells in the central nervous system (CNS). Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor transcription factor that regulates cell growth and differentiation. In this study we analyzed the influence of PPARγ agonists on neural stem cell growth and differentiation in culture. We found that in vitro culture of mouse NSCs in neurobasal medium with B27 in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) induced their growth and expansion as neurospheres. Addition of all-trans retinoic acid (ATRA) and PPARγ agonist ciglitazone or 15-Deoxy-Δ(12,14)-Prostaglandin J(2) (15d-PGJ2) resulted in a dose-dependent inhibition of cell viability and proliferation of NSCs in culture. Interestingly, NSCs cultured with PPARγ agonists, but not ATRA, showed significant increase in oligodendrocyte precursor-specific O4 and NG2 reactivity with a reduction in NSC marker nestin, in 3-7 days. In vitro treatment with PPARγ agonists and ATRA also induced modest increase in the expression of neuronal β-III tubulin and astrocyte-specific GFAP in NSCs in 3-7 days. Further analyses showed that PPARγ agonists and ATRA induced significant alterations in the expression of many stemness and differentiation genes associated with neuro-glial differentiation in NSCs. These findings highlight the influence of PPARγ agonists in promoting neuro-glial differentiation of NSCs and its significance in the treatment of neurodegenerative diseases.

Authors+Show Affiliations

Neuroscience Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, Indiana, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23185633

Citation

Kanakasabai, Saravanan, et al. "PPARγ Agonists Promote Oligodendrocyte Differentiation of Neural Stem Cells By Modulating Stemness and Differentiation Genes." PloS One, vol. 7, no. 11, 2012, pp. e50500.
Kanakasabai S, Pestereva E, Chearwae W, et al. PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes. PLoS ONE. 2012;7(11):e50500.
Kanakasabai, S., Pestereva, E., Chearwae, W., Gupta, S. K., Ansari, S., & Bright, J. J. (2012). PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes. PloS One, 7(11), e50500. https://doi.org/10.1371/journal.pone.0050500
Kanakasabai S, et al. PPARγ Agonists Promote Oligodendrocyte Differentiation of Neural Stem Cells By Modulating Stemness and Differentiation Genes. PLoS ONE. 2012;7(11):e50500. PubMed PMID: 23185633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes. AU - Kanakasabai,Saravanan, AU - Pestereva,Ecaterina, AU - Chearwae,Wanida, AU - Gupta,Sushil K, AU - Ansari,Saif, AU - Bright,John J, Y1 - 2012/11/21/ PY - 2012/03/20/received PY - 2012/10/23/accepted PY - 2012/11/28/entrez PY - 2012/11/28/pubmed PY - 2013/5/15/medline SP - e50500 EP - e50500 JF - PloS one JO - PLoS ONE VL - 7 IS - 11 N2 - Neural stem cells (NSCs) are a small population of resident cells that can grow, migrate and differentiate into neuro-glial cells in the central nervous system (CNS). Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor transcription factor that regulates cell growth and differentiation. In this study we analyzed the influence of PPARγ agonists on neural stem cell growth and differentiation in culture. We found that in vitro culture of mouse NSCs in neurobasal medium with B27 in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) induced their growth and expansion as neurospheres. Addition of all-trans retinoic acid (ATRA) and PPARγ agonist ciglitazone or 15-Deoxy-Δ(12,14)-Prostaglandin J(2) (15d-PGJ2) resulted in a dose-dependent inhibition of cell viability and proliferation of NSCs in culture. Interestingly, NSCs cultured with PPARγ agonists, but not ATRA, showed significant increase in oligodendrocyte precursor-specific O4 and NG2 reactivity with a reduction in NSC marker nestin, in 3-7 days. In vitro treatment with PPARγ agonists and ATRA also induced modest increase in the expression of neuronal β-III tubulin and astrocyte-specific GFAP in NSCs in 3-7 days. Further analyses showed that PPARγ agonists and ATRA induced significant alterations in the expression of many stemness and differentiation genes associated with neuro-glial differentiation in NSCs. These findings highlight the influence of PPARγ agonists in promoting neuro-glial differentiation of NSCs and its significance in the treatment of neurodegenerative diseases. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23185633/PPARγ_agonists_promote_oligodendrocyte_differentiation_of_neural_stem_cells_by_modulating_stemness_and_differentiation_genes_ L2 - http://dx.plos.org/10.1371/journal.pone.0050500 DB - PRIME DP - Unbound Medicine ER -