Next Generation Sequencing Facilities Quantitative analysis of hiPSC derived neural stem cells, early neural progenitors, neural progenitors and neural progenitors after exposure to Idebenone and Bezafibrate Transcriptomes. Next Generation Sequencing Facilities Quantitative analysis of hiPSC derived neural stem cells, early neural progenitors, neural progenitors and neural progenitors after exposure to Idebenone and Bezafibrate Transcriptomes

The mechanisms of neural differentiation of human induced pluripotent stem cells (hiPSCs) have been widely investigated, however the genes that play key regulatory role, especially involved in mitochondrial function are still unidentified. In this report transcriptome analysis of hiPSC differentiating into neural stem cells (NSC), early neural progenitors (eNP) and neural progenitors (NP) were performed. Gene Ontology and Network Analysis was implemented considering especially mitochondrial genes at all developmental stages and upon stimulation by idebenon (IDB) and bezafibrate (BZ) at NP stage. The genes strongly up-regulated during the process of differentiation in all tested stages belong mainly to: WNT; Cadherin and Gonadotropin-releasing hormone receptor signaling pathways. The interaction network shows that the transcription factors including HOXD3, ASCL1, HES5, and ZEB1 are possible key players in this process. Mitochondrial unfolded protein response (UPRmt), ROS defense, and pyruvate metabolism were the strongest up-regulated mitochondrial processes in all analyzed stages of neural differentiation. IDB and BZ treatment at NP stage induced different set of nuclear encoded mitochondrial genes involved in respiratory electron transport chain and fatty acid metabolic process respectively. Thus PARP agonist-mediated stimulation of mitochondrial genes influence the process of neural differentiation despite of mitochondrial biogenesis, but through the specific receptor pathways. Overall design: Examination of 3 stages of hiPSC neural differentation (neural stem cells - NSC, early neural progenitor - eNP, neural progenitor - NP) and response of hiPSC derived- neural progeniotors (NP) to Idebenone (IDB) or Bezafibrate (BZ). Three independant experiments of hiPSC neural differentation and NP treatment was performed. Analyzed 1 replicate from 3 independent neural differentation experiments and 1 replicate from 3 experiments related with drug exposure.