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Generation of induced neurons via direct conversion in vivo.

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Author

Summary, in English

Cellular reprogramming is a new and rapidly emerging field in which somatic cells can be turned into pluripotent stem cells or other somatic cell types simply by the expression of specific combinations of genes. By viral expression of neural fate determinants, it is possible to directly reprogram mouse and human fibroblasts into functional neurons, also known as induced neurons. The resulting cells are nonproliferating and present an alternative to induced pluripotent stem cells for obtaining patient- and disease-specific neurons to be used for disease modeling and for development of cell therapy. In addition, because the cells do not pass a stem cell intermediate, direct neural conversion has the potential to be performed in vivo. In this study, we show that transplanted human fibroblasts and human astrocytes, which are engineered to express inducible forms of neural reprogramming genes, convert into neurons when reprogramming genes are activated after transplantation. Using a transgenic mouse model to specifically direct expression of reprogramming genes to parenchymal astrocytes residing in the striatum, we also show that endogenous mouse astrocytes can be directly converted into neural nuclei (NeuN)-expressing neurons in situ. Taken together, our data provide proof of principle that direct neural conversion can take place in the adult rodent brain when using transplanted human cells or endogenous mouse cells as a starting cell for neural conversion.

Publishing year

2013

Language

English

Pages

7038-7043

Publication/Series

Proceedings of the National Academy of Sciences

Volume

110

Issue

17

Document type

Journal article

Publisher

National Academy of Sciences

Topic

  • Neurosciences

Status

Published

Project

  • Cell reprogramming: a new method for generating functional neurons

Research group

  • Developmental and Regenerative Neurobiology
  • Molecular Neurogenetics
  • Neurobiology

ISBN/ISSN/Other

  • ISSN: 1091-6490