title: Pioglitazone significantly prevented decreased rate of neural differentiation of mouse embryonic stem cells which was reduced by Pex11β knock-down.
abstract: Peroxisomes constitute special cellular organelles which display a variety of metabolic functions including fatty acid oxidation and free radical elimination. Abundance of these flexible organelles varies in response to different environmental stimuli. It has been demonstrated that PEX11β, a peroxisomal membrane elongation factor, is involved in the regulation of size, shape and number of peroxisomes. To investigate the role of PEX11β in neural differentiation of mouse embryonic stem cells (mESCs), we generated a stably transduced mESCs line that derives the expression of a short hairpin RNA against Pex11β gene following doxycycline (Dox) induction. Knock-down of Pex11β, during neural differentiation, significantly reduced the expression of neural progenitor cells and mature neuronal markers (p<0.05) indicating that decreased expression of PEX11β suppresses neuronal maturation. Additionally, mRNA levels of other peroxisome-related genes such as PMP70, Pex11α, Catalase, Pex19 and Pex5 were also significantly reduced by Pex11β knock-down (p<0.05). Interestingly, pretreatment of transduced mESCs with peroxisome proliferator-activated receptor γ agonist (pioglitazone (Pio)) ameliorated the inhibitory effects of Pex11β knock down on neural differentiation. Pio also significantly (p<0.05) increased the expression of neural progenitor and mature neuronal markers besides the expression of peroxisomal genes in transduced mESC. Results elucidated the importance of Pex11β expression in neural differentiation of mESCs, thereby highlighting the essential role of peroxisomes in mammalian neural differentiation. The observation that Pio recovered peroxisomal function and improved neural differentiation of Pex11β knocked-down mESCs, proposes a potential new pharmacological implication of Pio for neurogenesis in patients with peroxisomal defects.
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Esmaeili
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran; Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran. Electronic address: kamranghaedi@royaninstitute.org.
authors.forename: K
authors.initials: K
authors.lastname: Ghaedi
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Shoaraye Nejati
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Nematollahi
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Shiralyian
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address: mh_nasr@royaninstitute.org.
authors.forename: M H
authors.initials: MH
authors.lastname: Nasr-Esfahani
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists*; D020675:Peroxisomes / Q000187:drug effects* / Q000502:physiology; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D008565:Membrane Proteins; D047495:PPAR gamma; C490452:Pex11b protein, mouse; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: PEX11β; PPARγ; neural differentiation; peroxisome biogenesis; pioglitazone; shRNA