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Generation of induced neurons via direct conversion in vivo

Torper, Olof ; Pfisterer, Ulrich ; Wolf, Daniel A. ; Pereira, Maria ; Lau, Shong ; Jakobsson, Johan ; Björklund, Anders ; Grealish, Shane ; Parmar, Malin

Proceedings of the National Academy of Sciences - PNAS, 2013-04, Vol.110 (17), p.7038-7043 [Periódico revisado por pares]

Washington, DC: National Academy of Sciences

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Título:
Generation of induced neurons via direct conversion in vivo
Autor: Torper, Olof ; Pfisterer, Ulrich ; Wolf, Daniel A. ; Pereira, Maria ; Lau, Shong ; Jakobsson, Johan ; Björklund, Anders ; Grealish, Shane ; Parmar, Malin
Assuntos: Animals ; Astrocytes ; Astrocytes - cytology ; Astrocytes - transplantation ; Basic Medicine ; Biological and medical sciences ; Biological Sciences ; Brain ; Cell Differentiation - physiology ; Cells ; Cellular Reprogramming - drug effects ; Cellular Reprogramming - physiology ; Corpus Striatum - cytology ; Doxycycline - pharmacology ; Embryonic stem cells ; Fibroblasts ; Fibroblasts - cytology ; Fibroblasts - transplantation ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Genetic Vectors - genetics ; Green Fluorescent Proteins ; Humans ; Lentivirus ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; Mice ; Mice, Transgenic ; Neural stem cells ; Neuroglia ; Neurons ; Neurons - cytology ; Neurons - physiology ; Neurosciences ; Neurovetenskaper ; Pluripotent stem cells ; Rats ; Rats, Sprague-Dawley ; Rodents ; Somatic cells ; Tissue grafting ; Vertebrates: nervous system and sense organs
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2013-04, Vol.110 (17), p.7038-7043
Notas: http://dx.doi.org/10.1073/pnas.1303829110
1U.P. and D.A.W. contributed equally to this work.
Author contributions: O.T., U.P., D.A.W., J.J., A.B., S.G., and M. Parmar designed research; O.T., U.P., D.A.W., M. Pereira, S.L., and S.G. performed research; O.T., U.P., D.A.W., M. Pereira, S.L., J.J., A.B., S.G., and M. Parmar analyzed data; and M. Parmar wrote the paper.
Contributed by Anders Bjorklund, March 2, 2013 (sent for review January 27, 2013)
Descrição: 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.
Editor: Washington, DC: National Academy of Sciences
Idioma: Inglês

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Generation of induced neurons via direct conversion in vivo

Torper, Olof ; Pfisterer, Ulrich ; Wolf, Daniel A. ; Pereira, Maria ; Lau, Shong ; Jakobsson, Johan ; Björklund, Anders ; Grealish, Shane ; Parmar, Malin

Washington, DC: National Academy of Sciences

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