Materials and methods relating to neuronal development

C - Chemistry – Metallurgy – 12 – N

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C12N 5/0793 (2010.01) A61K 35/30 (2006.01) C12Q 1/02 (2006.01) G01N 33/50 (2006.01) G01N 33/566 (2006.01) A61K 35/12 (2006.01)

Patent

CA 2371260

The invention relates to the induction of the neuronal fate in neural stem cells or neural progenitor cells. The inventors have found that a neuronal fate in a neural stem cell or neural progenitor cell can be induced by expressing Nurr1 above basal levels within the cell. Nurr1 is a transcription factor of the thyroid hormone/retinoic acid nuclear receptor superfamily. It is shown herein that the expression of Nurr1 above basal levels in neural stem cells or neural progenitor cells increases the proportion of the cells which differentiate toward a neural fate. It has been found that in particular, dopaminergic neural stem cells or progenitor cells by a process including expression of Nurr1 above basal levels in the cells and contact of the cells with one or more factors supplied by or derived from Type I astrocytes of the ventral mesencephalon.

L'invention concerne l'induction du devenir neuronal dans des cellules neuronales souches ou dans des cellules progénitrices neuronales. Les inventeurs ont découvert que le devenir neuronal dans une cellule neuronale souche ou dans une cellule progénitrice neuronale pouvait être induit par expression de Nurr1 au-dessus de niveaux de base à l'intérieur de la cellule. Nurr1 représente un facteur de transcription de la superfamille des récepteurs des hormones thyroïdiennes/de l'acide rétinoïque nucléaire. Il a été démontré que l'expression de Nurr1 au-dessus de niveaux de base dans des cellules neuronales souches ou dans des cellules progénitrices neuronales augmente la proportion des cellules qui différencient le devenir neuronal, en particulier, pour les cellules neuronales souches dopaminergiques ou les cellules progénitrices, par un procédé comprenant l'expression de Nurr1 au-dessus de niveaux de base dans des cellules et par une mise en contact des cellules avec un ou plusieurs facteurs fournis par des astrocytes type 1 du mésencéphale ventral ou des dérivés de ceux-ci.

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