Comparative analysis of human embryonic stem cell-derived neural stem cells as an in vitro human model

Alternative cell models of human neural stem cells (hNSCs) have been developed and used for investigations ranging from in vitro experiments to in vivo clinical studies. However, a cell model capable of mimicking the ʻnormalʼ state of hNSCs is mandatory in order to extrapolate the results of these studies to humans. In the present study, to select a more suitable hNSC model for developing human-based experimental platforms, two representative hNSC types were compared, namely human embryonic stem cell (hESC)-derived hNSCs and ReNcell CX cells, which are well-characterized immortalized hNSC lines. The hNSCs, differentiated from hESCs via human neuroectodermal sphere (hNES) formation, recapitulated the molecular and cellular phenotypes of hNSCs, including NSC marker expression and terminal neuronal differentiation potential. Comparative analyses of the transcriptome profiles of the hESC-derived hNESs and ReNcell CX hNSCs showed that the differentiated hNESs were analogous to the ReNcell CX cells, as demonstrated by principal component analysis and hierarchical sample clustering. The hNSC-specific transcriptome was presented, comprising commonly expressed transcripts between hNESs derived from hESCs and ReNcell CX cells. To elucidate the molecular mechanisms associated with the hNSC identity, the hNSC-specific transcriptome was analyzed using pathway and functional annotation clustering analyses. The results suggested that hESC-derived hNESs, an expandable and accessible cell source, may be used as a relevant hNSC model in a wide range of neurological investigations.