title: Embryonic stem-derived versus somatic neural stem cells: a comparative analysis of their developmental potential and molecular phenotype.
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.
authors.affiliation: Stem Cell Research Department, Dipartmento di Biotecnologie, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Colombo
authors.forename: Serena G
authors.initials: SG
authors.lastname: Giannelli
authors.forename: Rossella
authors.initials: R
authors.lastname: Galli
authors.forename: Enrico
authors.initials: E
authors.lastname: Tagliafico
authors.forename: Chiara
authors.initials: C
authors.lastname: Foroni
authors.forename: Elena
authors.initials: E
authors.lastname: Tenedini
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Giorgio
authors.initials: G
authors.lastname: Corte
authors.forename: Angelo
authors.initials: A
authors.lastname: Vescovi
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.forename: Vania
authors.initials: V
authors.lastname: Broccoli
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D020869:Gene Expression Profiling; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D039901:Totipotent Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D007335:Insulin-Like Growth Factor II