Sensitivity of hiPSC-derived neural stem cells (NSC) to Pyrroloquinoline quinone depends on their developmental stage.

Toxicol In Vitro. 2017 May 31. pii: S0887-2333(17)30133-9. doi: 10.1016/j.tiv.2017.05.017. [Epub ahead of print]

Sensitivity of hiPSC-derived neural stem cells (NSC) to Pyrroloquinoline quinone depends on their developmental stage.

Augustyniak J1, Lenart J2, Zychowicz M1, Lipka G1, Gaj P3, Kolanowska M4, Stepien PP5, Buzanska L6.

Author information

1 Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Poland.

2 Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Poland.

3 Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland.

4 Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland; Genomic Medicine, Medical University of Warsaw, Warsaw, Poland.

5 Department of Genetics, Faculty of Biology, University of Warsaw, Poland; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw; Centre for New Technologies, University of Warsaw, Poland.

6 Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Poland. Electronic address: Ten adres pocztowy jest chroniony przed spamowaniem. Aby go zobaczyć, konieczne jest włączenie w przeglądarce obsługi JavaScript..

ABSTRACT

Pyrroloquinoline quinone (PQQ) is a factor influencing on the mitochondrial biogenesis. In this study the PQQ effect on viability, total cell number, antioxidant capacity, mitochondrial biogenesis and differentiation potential was investigated in human induced Pluripotent Stem Cells (iPSC) - derived: neural stem cells (NSC), early neural progenitors (eNP) and neural progenitors (NP). Here we demonstrated that sensitivity to PQQ is dependent upon its dose and neural stage of development. Induction of the mitochondrial biogenesis by PQQ at three stages of neural differentiation was evaluated at mtDNA, mRNA and protein level. Changes in NRF1, TFAM and PPARGC1A gene expression were observed at all developmental stages, but only at eNP were correlated with the statistically significant increase in the mtDNA copy numbers and enhancement of SDHA, COX-1 protein level. Thus, the "developmental window" of eNP for PQQ-evoked mitochondrial biogenesis is proposed. This effect was independent of high antioxidant capacity of PQQ, which was confirmed in all tested cell populations, regardless of the stage of hiPSC neural differentiation. Furthermore, a strong induction of GFAP, with down regulation of MAP2 gene expression upon PQQ treatment was observed. This indicates a possibility of shifting the balance of cell differentiation in the favor of astroglia, but more research is needed at this point.

KEYWORDS:

Developmental neurotoxicity; Mitochondrial biogenesis; Neural progenitors; Neural stem cells; PQQ; hiPSC

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