title: Direct neural conversion from human fibroblasts using self-regulating and nonintegrating viral vectors.
abstract: Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy.
authors.affiliation: Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, BMC A11, 221 84 Lund, Sweden.
authors.forename: Shong
authors.initials: S
authors.lastname: Lau
authors.affiliation: Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, BMC A11, 221 84 Lund, Sweden.
authors.forename: Daniella
authors.initials: D
authors.lastname: Rylander Ottosson
authors.affiliation: Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, BMC A11, 221 84 Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Jakobsson
authors.affiliation: Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, BMC A11, 221 84 Lund, Sweden. Electronic address: malin.parmar@med.lu.se.
authors.forename: Malin
authors.initials: M
authors.lastname: Parmar
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D034622:RNA Interference; D014161:Transduction, Genetic
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs