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EMBRYONIC STEM CELLS

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

^a Stem Cell Research Department, San Raffaele Scientific Institute, Milan, Italy;
^b Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy;
^c National Institute for Cancer Research, Genoa, Italy;
^d Department of Oncology, Biology and Genetics, Genova University Medical School, Genova, Italy

Key Words. Neural stem cell • Embryonic stem cell • Neural differentiation • Self-renewal • Multipotency • Transcriptional profile

Correspondence: Vania Broccoli, Ph.D., Stem Cell Research Department, Dipartmento di Biotecnologie, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. Telephone: +39 02 26434612; Fax: +39 02 26434621; e-mail: broccoli.vania{at}hsr.it

Received on July 12, 2005; accepted for publication on December 5, 2005.

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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