title: Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells.
abstract: Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphology and global gene expression profile consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelin. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Fadi J
authors.initials: FJ
authors.lastname: Najm
authors.forename: Angela M
authors.initials: AM
authors.lastname: Lager
authors.forename: Anita
authors.initials: A
authors.lastname: Zaremba
authors.forename: Krysta
authors.initials: K
authors.lastname: Wyatt
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Caprariello
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Factor
authors.forename: Robert T
authors.initials: RT
authors.lastname: Karl
authors.forename: Tadao
authors.initials: T
authors.lastname: Maeda
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tesar
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D024861:Genetic Enhancement / Q000379:methods; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014157:Transcription Factors