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Generation of induced neurons via direct conversion in vivo.

Torper, Olof LU ; Pfisterer, Ulrich LU ; Wolf, Daniel LU ; Pereira, Maria J M LU ; Lau, Shong LU ; Jakobsson, Johan LU ; Björklund, Anders LU ; Grealish, Shane LU and Parmar, Malin LU (2013) In Proceedings of the National Academy of Sciences 110(17). p.7038-7043
Abstract
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... (More)
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. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
110
issue
17
pages
7038 - 7043
publisher
National Acad Sciences
external identifiers
  • wos:000318677300090
  • pmid:23530235
  • scopus:84876667526
ISSN
1091-6490
DOI
10.1073/pnas.1303829110
language
English
LU publication?
yes
id
4b5db5d0-c1b6-463c-9ca2-f61b01429744 (old id 3627659)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23530235?dopt=Abstract
date added to LUP
2013-04-02 13:19:55
date last changed
2019-04-23 01:28:18
@article{4b5db5d0-c1b6-463c-9ca2-f61b01429744,
  abstract     = {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.},
  author       = {Torper, Olof and Pfisterer, Ulrich and Wolf, Daniel and Pereira, Maria J M and Lau, Shong and Jakobsson, Johan and Björklund, Anders and Grealish, Shane and Parmar, Malin},
  issn         = {1091-6490},
  language     = {eng},
  number       = {17},
  pages        = {7038--7043},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Generation of induced neurons via direct conversion in vivo.},
  url          = {http://dx.doi.org/10.1073/pnas.1303829110},
  volume       = {110},
  year         = {2013},
}