title: Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.
abstract: Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology to understand the biology of myelin diseases and to develop treatments for such disorders. Here, we demonstrate that the induction of three transcription factors (SOX10, OLIG2, NKX6.2) in iPSC-derived neural progenitor cells is sufficient to rapidly generate O4+OL with an efficiency of up to 70% in 28 d and a global gene-expression profile comparable to primary human OL. We further demonstrate that iPSC-derived OL disperse and myelinate the CNS ofMbpshi/shiRag-/-mice during development and after demyelination, are suitable for in vitro myelination assays, disease modeling, and screening of pharmacological compounds potentially promoting oligodendroglial differentiation. Thus, the strategy presented here to generate OL from iPSC may facilitate the studying of human myelin diseases and the development of high-throughput screening platforms for drug discovery.
authors.affiliation: Institute of Neuropathology, University Hospital Münster, 48149 Muenster, Germany.|Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Ehrlich
authors.affiliation: INSERM, U1127, F-75013 Paris, France.|CNRS, UMR 7225, F-75013 Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UM-75, F-75005 Paris, France.|Institut du Cerveau et de la Moelle epinière-Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.
authors.forename: Sabah
authors.initials: S
authors.lastname: Mozafari
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Glatza
authors.affiliation: Institute of Neuropathology, University Hospital Münster, 48149 Muenster, Germany.|Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Starost
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Sergiy
authors.initials: S
authors.lastname: Velychko
authors.affiliation: Institute of Neuropathology, University Hospital Münster, 48149 Muenster, Germany.|Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Hallmann
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4.
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Cui
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Kee-Pyo
authors.initials: KP
authors.lastname: Kim
authors.affiliation: INSERM, U1127, F-75013 Paris, France.|CNRS, UMR 7225, F-75013 Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UM-75, F-75005 Paris, France.|Institut du Cerveau et de la Moelle epinière-Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Bachelin
authors.affiliation: INSERM, U1127, F-75013 Paris, France.|CNRS, UMR 7225, F-75013 Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UM-75, F-75005 Paris, France.|Institut du Cerveau et de la Moelle epinière-Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Marteyn
authors.affiliation: Institute of Neuropathology, University Hospital Münster, 48149 Muenster, Germany.|Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hargus
authors.affiliation: Department of Physiology, McGill University, Montreal, QC, Canada H3A 2B4.
authors.forename: Radia Marie
authors.initials: RM
authors.lastname: Johnson
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4.
authors.forename: Jack
authors.initials: J
authors.lastname: Antel
authors.affiliation: DFG Research Center for Regenerative Therapies, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Jared
authors.initials: J
authors.lastname: Sterneckert
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.|Medical Faculty, Department of Anatomy and Molecular Embryology, Ruhr-University Bochum, 44801 Bochum, Germany.
authors.forename: Holm
authors.initials: H
authors.lastname: Zaehres
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.|Medicial Faculty, Westphalian Wilhelms-University of Muenster, 48149 Muenster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: INSERM, U1127, F-75013 Paris, France.|CNRS, UMR 7225, F-75013 Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Paris 06, UM-75, F-75005 Paris, France.|Institut du Cerveau et de la Moelle epinière-Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Baron-Van Evercooren
authors.affiliation: Institute of Neuropathology, University Hospital Münster, 48149 Muenster, Germany; Tanja.Kuhlmann@ukmuenster.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuhlmann
mesh_terms: D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D016000:Cluster Analysis; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000066630:Ectopic Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D018384:Oxidative Stress; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004676:Myelin Basic Protein; D014157:Transcription Factors; D016875:tau Proteins
keywords: disease modeling; forward patterning; human iPSC; myelination; oligodendrocytes