title: Generation of induced neurons via direct conversion in vivo.
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.
authors.affiliation: Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 221 84 Lund, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Torper
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pfisterer
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Wolf
authors.forename: Maria
authors.initials: M
authors.lastname: Pereira
authors.forename: Shong
authors.initials: S
authors.lastname: Lau
authors.forename: Johan
authors.initials: J
authors.lastname: Jakobsson
authors.forename: Anders
authors.initials: A
authors.lastname: Björklund
authors.forename: Shane
authors.initials: S
authors.lastname: Grealish
authors.forename: Malin
authors.initials: M
authors.lastname: Parmar
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000637:transplantation*; D002454:Cell Differentiation / Q000502:physiology*; D065150:Cellular Reprogramming / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology; D004318:Doxycycline / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000637:transplantation*; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins; D006801:Humans; D016086:Lentivirus; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D049452:Green Fluorescent Proteins; D004318:Doxycycline