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Biogerontology. 2017 Aug;18(4):665-677. doi: 10.1007/s10522-017-9718-4. Epub 2017 Jun 22.

Mitochondrial biogenesis and neural differentiation of human iPSC is modulated by idebenone in a developmental stage-dependent manner.

Author information

1
Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
2
Department of Neurochemistry, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
3
Department of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
4
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
5
Centre of New Technologies, University of Warsaw, Warsaw, Poland.
6
Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland. buzanska@imdk.pan.pl.

Abstract

Idebenone, the synthetic analog of coenzyme Q10 can improve electron transport in mitochondria. Therefore, it is used in the treatment of Alzheimer's disease and other cognitive impairments. However, the mechanism of its action on neurodevelopment is still to be elucidated. Here we demonstrate that the cellular response of human induced pluripotent stem cells (hiPSC) to idebenone depends on the stage of neural differentiation. When: neural stem cells (NSC), early neural progenitors (eNP) and advanced neural progenitors (NP) have been studied a significant stimulation of mitochondrial biogenesis was observed only at the eNP stage of development. This coexists with the enhancement of cell viability and increase in total cell number. In addition, we report novel idebenone properties in a possible regulation of neural stem cells fate decision: only eNP stage responded with up-regulation of both neuronal (MAP2), astrocytic (GFAP) markers, while at NSC and NP stages significant down-regulation of MAP2 expression was observed, promoting astrocyte differentiation. Thus, idebenone targets specific stages of hiPSC differentiation and may influence the neural stem cell fate decision.

KEYWORDS:

Astrocytic differentiation; Developmental neurotoxicity; Idebenone; Mitochondrial biogenesis; Neural progenitors; Neuronal; hiPSC; mtDNA copy number

PMID:
28643190
PMCID:
PMC5514205
DOI:
10.1007/s10522-017-9718-4
[Indexed for MEDLINE]
Free PMC Article

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