title: Direct conversion of human fibroblasts into dopaminergic neural progenitor-like cells using TAT-mediated protein transduction of recombinant factors.
abstract: Recent progress in the generation of induced neural progenitor cells (iNPCs) holds tremendous potential for regenerative medicine. However, a major limitation is the lack of a reliable source for cell replacement therapy in neurological diseases such as Parkinson's disease (PD). Here, we show that the combination of small molecules (SM) and TAT-mediated protein transduction of SOX2 and LMX1a in a 3D sphere culture directly convert human fibroblasts to induced dopaminergic neural progenitor-like cells (iDPCs). The generated iDPCs expressed various NPC markers (SOX2, PAX6, NESTIN, OLIG2) and midbrain progenitor markers (EN1, LMX1a, FOXA2, WNT1) as detected by immunostaining and real-time PCR. Following differentiation, the majority of cells expressed neuronal dopaminergic markers as indicated by co-expression of TH with NURR1, and/or PITX3. We found that SOX2 and LMX1a TAT-mediated protein transduction in the combination of SM could directly convert human fibroblasts to self-renewal iDPCs. In conclusion, to our best knowledge, this is the first report of generation of safe DPCs and may suggest an alternative strategy for cell therapy for the treatment of neurodegenerative disorders.
authors.affiliation: School of Biology, College of Science, Tehran University, P.O. Box 14155-6455, Tehran, Iran; Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, 1998777494, Tehran, Iran. Electronic address: mirakhori@ut.ac.ir.
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Mirakhori
authors.affiliation: School of Biology, College of Science, Tehran University, P.O. Box 14155-6455, Tehran, Iran. Electronic address: bzeynali@khayam.ut.ac.ir.
authors.forename: Bahman
authors.initials: B
authors.lastname: Zeynali
authors.affiliation: Department of Molecular Systems Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran. Electronic address: rassouli59@gmail.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rassouli
authors.affiliation: Department of Molecular Systems Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran. Electronic address: hsalekdeh@yahoo.com.
authors.forename: Ghasem Hosseini
authors.initials: GH
authors.lastname: Salekdeh
authors.affiliation: School of Biology, College of Science, Tehran University, P.O. Box 14155-6455, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, ACECR, P.O. Box 19395-4644, Tehran, Iran. Electronic address: baharvand@royaninstitute.org.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D058953:Neural Stem Cells / Q000378:metabolism*; D021381:Protein Transport; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D004298:Dopamine
keywords: Human fibroblasts; Induced dopaminergic neural progenitor-like cells; Protein transduction; Small molecules