Embryonic stem cells neural differentiation qualifies the role of Wnt/β-Catenin signals in human telencephalic specification and regionalization
| Autor: | Aurore Bugi, Christine Varela, Laetitia Aubry, Camille Nicoleau, Yves Maury, Fany Bourgois-Rocha, Pedro Viegas, Anselme L. Perrier, Marc Peschanski, Caroline Bonnefond |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Telencephalon
Biology 03 medical and health sciences Mice 0302 clinical medicine Animals Humans Hedgehog Proteins Progenitor cell Sonic hedgehog Induced pluripotent stem cell Wnt Signaling Pathway Embryonic Stem Cells 030304 developmental biology Body Patterning Neurons 0303 health sciences Wnt signaling pathway Cell Differentiation Cell Biology Anatomy Embryonic stem cell Rats Transplantation Huntington Disease Organ Specificity biology.protein Molecular Medicine Stem cell Neuroscience Developmental biology Heterocyclic Compounds 3-Ring 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | STEM CELLS |
| ISSN: | 1066-5099 |
| DOI: | 10.1002/stem.1462 |
| Popis: | Wnt-ligands are among key morphogens that mediate patterning of the anterior territories of the developing brain in mammals. We qualified the role of Wnt-signals in regional specification and subregional organization of the human telencephalon using human pluripotent stem cells (hPSCs). One step neural conversion of hPSCs using SMAD inhibitors leads to progenitors with a default rostral identity. It provides an ideal biological substrate for investigating the role of Wnt signaling in both anteroposterior and dorso-ventral processes. Challenging hPSC-neural derivatives with Wnt-antagonists, alone or combined with sonic hedgehog (Shh), we found that Wnt-inhibition promote both telencephalic specification and ventral patterning of telencephalic neural precursors in a dose-dependent manner. Using optimal Wnt-antagonist and Shh-agonist signals we produced human ventral-telencephalic precursors, committed to differentiation into striatal projection neurons both in vitro and in vivo after homotypic transplantation in quinolinate-lesioned rats. This study indicates that sequentially organized Wnt-signals play a key role in the development of human ventral telencephalic territories from which the striatum arise. In addition, the optimized production of hPSC-derived striatal cells described here offers a relevant biological resource for exploring and curing Huntington disease. |
| Databáze: | OpenAIRE |
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