Embryonic Stem-Derived Versus Somatic Neural Stem Cells: A Comparative Analysis of Their Developmental Potential and Molecular Phenotype

Stem Cell Research Department, Dipartmento di Biotecnologie, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Stem Cells (Impact Factor: 7.13). 05/2006; 24(4):825-34. DOI: 10.1634/stemcells.2005-0313
Source: PubMed

ABSTRACT Reliable procedures to induce neural commitment of totipotent undifferentiated embryonic stem (ES) cells have provided new tools for investigating the molecular mechanisms underlying cell fate choices. We extensively characterized the developmental potential of ES-induced neural cells obtained using an adaptation of the multistep induction protocol. We provided evidence that ES-derived neural proliferating cells are endowed with stem cell properties such as extensive self-renewal capacity and single-cell multipotency. In differentiating conditions, cells matured exclusively into neurons, astrocytes, and oligodendrocytes. All these features have been previously described in only somatic neural stem cells (NSCs). Therefore, we consider it more appropriate to rename our cells ES-derived NSCs. These similarities between the two NSC populations induced us to carefully compare their proliferation ability and differentiation potential. Although they were very similar in overall behavior, we scored specific differences. For instance, ES-derived NSCs proliferated at higher rate and consistently generated a higher number of neurons compared with somatic NSCs. To further investigate their relationships, we carried out a molecular analysis comparing their transcriptional profiles during proliferation. We observed a large fraction of shared expressed transcripts, including genes previously described to be critical in defining somatic NSC traits. Among the genes differently expressed, candidate genes possibly responsible for divergences between the two cell types were selected and further investigated. In particular, we showed that an enhanced MAPK (mitogen-activated protein kinase) signaling is acting in ES-induced NSCs, probably triggered by insulin-like growth factor-II. This may contribute to the high proliferation rate exhibited by these cells in culture.

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Available from: Sergio Ferrari, Sep 26, 2014
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    • "NPCs derived from ESCs were cultured in medium containing 20 ng/mL EGF and 10 ng/mL FGF2 as previously described (Colombo et al. 2006). Zrf1 and Pax6 re-expression was obtained by electropoating pCBA Zrf1 3xFlag and pCBA Pax6 3xFlag (Amaxa neural stem cell kit), and selected with neomycin for 6 d. "
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    • "The strength of this method is the relative purity of the final product and the ability to generate large numbers of NSCs upon FGF2 addition , whereas weaknesses include the extended time it takes to generate NSCs, 10 days to two weeks, and the variability in the quality of the final product, which can be contaminated with mesodermal derivatives, likely due to the multiple steps. An accelerated version of this approach, which combines the selection and proliferation steps, produces a similar end product (Colombo et al., 2006). The embryoid body selection protocol has also been applied to the derivation of neurons from human as well as mouse ESCs (Carpenter et al., 2001; Zhang et al., 2001). "
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