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

Abstract

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.

TAZ Represses the Neuronal Commitment of Neural Stem Cells

“…Considering that the dynamics of the NSPCs are most likely influenced by local niche factors, and the outcome on stemness, proliferation, and differentiation, is region-, age-, and cell-specific, in order to analyze the mechanistic regulation of NSPCs by TAZ in a general context, we used the midbrain-derived immortalized NSPC line ReNcell VM. These cells are an excellent tool to replicate, in a non-animal model, and, under controlled non-autonomous signals, the evolution of neurogenesis [ 41 , 42 , 43 , 44 ]. Under stem growth conditions (in the presence of growth factors), these cells expressed TAZ and also the NSPCs marker, Nestin, similar to the NSPCs of the neurogenic niches ( Figure 3 A).…”

Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids

“…The H9 human embryonic stem cell (hESC) line was purchased from the WiCell Research Institute (Madison, WI, USA). Fibroblasts and hPSCs, including hESCs and hiPSCs, were cultured as described previously 47 . Integration-free hiPSCs were generated from fibroblasts using Episomal iPSC Reprogramming Vectors (Cat.…”

In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

“…Neuronal stem cells were used to study pathogenic changes in the expression of the DISC1 gene, which is important in the development of SZ. Application of the NSC model in in vitro studies allows for investigation of the molecular functions of susceptibility genes for SZ [62,66,67].…”