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Original Article |
1 Stem Cell Research Department, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
2 Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 441100 Modena, Italy
3 National Institute for Cancer Research, 16132 Genoa, Italy
* To whom correspondence should be addressed. E-mail: broccoli.vania{at}hsr.it.
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Abstract |
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Reliable procedures to induce neural commitment of totipotent undifferentiated embryonic stem (ES) cells have provided new tools to investigate the molecular mechanisms underlying cell fate choices. We extensively characterized the developmental potential of ES induced neural cells obtained using an adaptation of the multi-step induction protocol [1]. We provided evidences 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 only in somatic neural stem cells (NSCs). Therefore, we consider more appropriate to rename our cells ES derived NSCs. These similarities between the two NSCs populations induced us to carefully compare their proliferation ability and differentiation potential. Although, very similar in overall behaviour, we scored specific differences. For instance, ES derived NSCs proliferated at higher rate and generated consistently a higher number of neurons compared to somatic NSCs. To further investigate their relationships, we carried out a molecular analysis comparing their transcriptional profiles during proliferation. A large fraction of shared expressed transcripts was observed 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 signalling is acting in ES induced NSCs probably triggered by IGF-II. This may contribute to the high proliferation rate exhibited by these cells in culture.
Key Words. neural stem cell, embryonic stem cell, neural differentiation, self-renewal, multipotency, transcriptional profile
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