Mizuseki, K. et al. Generation of neural crest-derived peripheral neurons and floor plate cells from mouse and primate embryonic stem cells. Proc. Natl Acad. Sci. USA 100, 5828-5833

Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047 Japan.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 06/2003; 100(10):5828-33. DOI: 10.1073/pnas.1037282100
Source: PubMed

ABSTRACT To understand the range of competence of embryonic stem (ES) cell-derived neural precursors, we have examined in vitro differentiation of mouse and primate ES cells into the dorsal- (neural crest) and ventralmost (floor plate) cells of the neural axis. Stromal cell-derived inducing activity (SDIA; accumulated on PA6 stromal cells) induces cocultured ES cells to differentiate into rostral CNS tissues containing both ventral and dorsal cells. Although early exposure of SDIA-treated ES cells to bone morphogenetic protein (BMP)4 suppresses neural differentiation and promotes epidermogenesis, late BMP4 exposure after the fourth day of coculture causes differentiation of neural crest cells and dorsalmost CNS cells, with autonomic system and sensory lineages induced preferentially by high and low BMP4 concentrations, respectively. In contrast, Sonic hedgehog (Shh) suppresses differentiation of neural crest lineages and promotes that of ventral CNS tissues such as motor neurons. Notably, high concentrations of Shh efficiently promote differentiation of HNF3beta(+) floor plate cells with axonal guidance activities. Thus, SDIA-treated ES cells generate naive precursors that have the competence of differentiating into the "full" dorsal-ventral range of neuroectodermal derivatives in response to patterning signals.

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Available from: Akiko Arakawa, Aug 22, 2015
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    • "Embryonic stem cells, established from the ICM of blastocyst, can differentiate into all kinds of embryonic tissues, mimicking the pluripotent nature of the origin. Over the last decade, numerous studies have demonstrated steered differentiation of embryonic stem (ES) cells into various tissues by mimicking the signaling environments of the early embryo (Wichterle et al. 2002; Mizuseki et al. 2003; Gotz & Barde 2005; Murry & Keller 2008; Yeo et al. 2008; Zhang et al. 2008). A straightforward application of these techniques is to use these differentiated cells for regenerative medicine and drug discovery. "
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    ABSTRACT: Embryonic stem (ES) cells have been successfully used over the past decade to generate specific types of neuronal cells. In addition to its value for regenerative medicine, ES cell culture also provides versatile experimental systems for analyzing early neural development. These systems are complimentary to conventional animal models, particularly because they allow unique constructive (synthetic) approaches, for example, step-wise addition of components. Here we review the ability of ES cells to generate not only specific neuronal populations but also functional neural tissues by recapitulating microenvironments in early mammalian development. In particular, we focus on cerebellar neurogenesis from mouse ES cells, and explain the basic ideas for positional information and self-formation of polarized neuroepithelium. Basic research on developmental signals has fundamentally contributed to substantial progress in stem cell technology. We also discuss how in vitro model systems using ES cells can shed new light on the mechanistic understanding of organogenesis, taking an example of recent progress in self-organizing histogenesis.
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    • "Another important strategy to enhance the differentiation toward neuron lineage is coculture of ESCs with stromal cell lines such as PA6 (Kawasaki et al., 2000) and MS5 (Barberi et al., 2003). This effect of PA6 cells has been named the inductive factor stromal cell-derived inducing activity (SDIA) (Mizusekiet et al., 2003; Kawasaki et al., 2000). After screening various cell lines, Kawasaki et al found that PA6 stromal cells derived from mouse skull bone marrow is a potent inducer of neural differentiation from ESCs (Figure 2). "
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    • "Sox10þ/Kitþ cells isolated from the E10.5 embryonic neural tube generated TuJ-1-positive N under those conditions, as did Sox10þ/KitÀ cells (Fig. 7A, B, Table 1), indicating that Sox10þ/Kitþ cells have the potential to differentiate into N similar to the Sox10þ/KitÀ cells, which correspond to ventrally migrating NC cells. Furthermore , we cultured Sox10þ/Kitþ cells on PA6 stromal cells according to Mizuseki et al. (2003), and found that these Sox10þ/Kitþ cells also generated TuJ-1-positive N and GFAP-positive G (Fig. 7C–E, Table 1 "
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    ABSTRACT: Multipotency of neural crest cells (NC cells) is thought to be a transient phase at the early stage of their generation; after NC cells emerge from the neural tube, they are specified into the lineage-restricted precursors. We analyzed the differentiation of early-stage NC-like cells derived from Sox10-IRES-Venus ES cells, where the expression of Sox10 can be visualized with a fluorescent protein. Unexpectedly, both the Sox10+/Kit- cells and the Sox10+/Kit+ cells, which were restricted in vivo to the neuron (N)-glial cell (G) lineage and melanocyte (M) lineage, respectively, generated N, G, and M, showing that they retain multipotency. We generated mice from the Sox10-IRES-Venus ES cells and analyzed the differentiation of their NC cells. Both the Sox10+/Kit- cells and Sox10+/Kit+ cells isolated from these mice formed colonies containing N, G, and M, showing that they are also multipotent. These findings suggest that NC cells retain multipotency even after the initial lineage-restricted stages.
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