title: Functional characterization of Friedreich ataxia iPS-derived neuronal progenitors and their integration in the adult brain.
abstract: Friedreich ataxia (FRDA) is an autosomal recessive disease characterised by neurodegeneration and cardiomyopathy that is caused by an insufficiency of the mitochondrial protein, frataxin. Our previous studies described the generation of FRDA induced pluripotent stem cell lines (FA3 and FA4 iPS) that retained genetic characteristics of this disease. Here we extend these studies, showing that neural derivatives of FA iPS cells are able to differentiate into functional neurons, which don't show altered susceptibility to cell death, and have normal mitochondrial function. Furthermore, FA iPS-derived neural progenitors are able to differentiate into functional neurons and integrate in the nervous system when transplanted into the cerebellar regions of host adult rodent brain. These are the first studies to describe both in vitro and in vivo characterization of FA iPS-derived neurons and demonstrate their capacity to survive long term. These findings are highly significant for developing FRDA therapies using patient-derived stem cells.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia; Centre for Neural Engineering, Department of Electrical and Electronic Engineering, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bird
authors.affiliation: Department of Otolaryngology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Karina
authors.initials: K
authors.lastname: Needham
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Frazier
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jorien
authors.initials: J
authors.lastname: van Rooijen
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jessie
authors.initials: J
authors.lastname: Leung
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Shelley
authors.initials: S
authors.lastname: Hough
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Denham
authors.affiliation: Division of Maternal Fetal Medicine, Saban Research Institute of Children's Hospital of Los Angeles, Los Angeles, California, United States of America.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Thornton
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Parish
authors.affiliation: Department of Audiology and Speech Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Bryony A
authors.initials: BA
authors.lastname: Nayagam
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Pera
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia; Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Victoria, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Thorburn
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Lachlan H
authors.initials: LH
authors.lastname: Thompson
authors.affiliation: Centre for Neural Engineering, Department of Electrical and Electronic Engineering, The University of Melbourne, Melbourne, Victoria, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Mirella
authors.initials: M
authors.lastname: Dottori
mesh_terms: D000328:Adult; D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D002531:Cerebellum / Q000166:cytology*; D005260:Female; D005621:Friedreich Ataxia / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D033862:Iron-Binding Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin