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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2018 (publ. 2017, arch)     Display Documents



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ID: 744157.0, MPI für molekulare Biomedizin / Jahrbuch 2018 (publ. 2017, arch)
Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors
Authors:Ehrlich, M.; Mozafari, S.; Glatza, M.; Starost, L.; Velychko, S.; Hallmann, A. L.; Cui, Q. L.; Schambach, A.; Kim, K. P.; Bachelin, C.; Marteyn, A.; Hargus, G.; Johnson, R. M.; Antel, J.; Sterneckert, J.; Zaehres, H.; Scholer, H. R.; Baron-Van Evercooren, A.; Kuhlmann, T.
Date of Publication (YYYY-MM-DD):2017-03-14
Title of Journal:Proc Natl Acad Sci u S A
Volume:114
Issue / Number:11
Start Page:E2243
End Page:E2252
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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 of Mbp(shi/shi)Rag(-/-) 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.
Free Keywords:Animals; Biomarkers; Brain/metabolism/pathology/ultrastructure; Cell Death/genetics; Cell Differentiation/*genetics; Cell Lineage/genetics; Cells, Cultured; Cluster Analysis; Demyelinating Diseases/genetics/metabolism/pathology; Disease Models, Animal; Ectopic Gene Expression; Gene Expression Profiling; Humans; Induced Pluripotent Stem Cells/*cytology/*metabolism; Mice; Mutation; Myelin Basic Protein/genetics/metabolism; Myelin Sheath/genetics/metabolism; Neural Stem Cells/cytology/metabolism; Oligodendroglia/*cytology/*metabolism; Oxidative Stress; Spinal Cord/metabolism/pathology/ultrastructure; Transcription Factors/*genetics/metabolism; Transcriptome; tau Proteins/genetics/metabolism; *disease modeling; *forward patterning; *human iPSC; *myelination; *oligodendrocytes
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:MPI für molekulare Biomedizin
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany. INSERM, U1127, F-75013 Paris, France. CNRS, UMR 7225, F-75013 Paris, France. Sorbonne Universites, Universite Pierre et Marie Curie Paris 06, UM-75, F-75005 Paris, France. Institut du Cerveau et de la Moelle epiniere-Groupe Hospitalier Pitie-Salpetriere, F-75013 Paris, France. Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4. Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany. Department of Physiology, McGill University, Montreal, QC, Canada H3A 2B4. DFG Research Center for Regenerative Therapies, Technische Universitat Dresden, 01307 Dresden, Germany. Medical Faculty, Department of Anatomy and Molecular Embryology, Ruhr-University Bochum, 44801 Bochum, Germany. Medicial Faculty, Westphalian Wilhelms-University of Muenster, 48149 Muenster, Germany. Institute of Neuropathology, University Hospital Munster, 48149 Muenster, Germany; Tanja.Kuhlmann@ukmuenster.de.
Identifiers:ISSN:1091-6490 (Electronic) 0027-8424 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/28246330 [ID No:2]
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