Abstract
Oligodendrocytes are the myelinating glia of the central nervous system and ensure rapid saltatory conduction. Shortage or loss of these cells leads to severe malfunctions as observed in human leukodystrophies and multiple sclerosis, and their replenishment by reprogramming or cell conversion strategies is an important research aim. Using a transgenic approach we increased levels of the transcription factor Sox10 throughout the mouse embryo and thereby prompted Fabp7-positive glial cells in dorsal root ganglia of the peripheral nervous system to convert into cells with oligodendrocyte characteristics including myelin gene expression. These rarely studied and poorly characterized satellite glia did not go through a classic oligodendrocyte precursor cell stage. Instead, Sox10 directly induced key elements of the regulatory network of differentiating oligodendrocytes, including Olig2, Olig1, Nkx2.2 and Myrf. An upstream enhancer mediated the direct induction of the Olig2 gene. Unlike Sox10, Olig2 was not capable of generating oligodendrocyte-like cells in dorsal root ganglia. Our findings provide proof-of-concept that Sox10 can convert conducive cells into oligodendrocyte-like cells in vivo and delineates options for future therapeutic strategies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Cell Differentiation / genetics*
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Central Nervous System / metabolism*
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Central Nervous System / pathology
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Embryo, Mammalian
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Fatty Acid-Binding Protein 7
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Fatty Acid-Binding Proteins / genetics
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Homeobox Protein Nkx-2.2
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Homeodomain Proteins / genetics
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Humans
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Mice
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Multiple Sclerosis / genetics*
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Multiple Sclerosis / pathology
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Nerve Tissue Proteins / genetics
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Neuroglia
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Nuclear Proteins
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Oligodendrocyte Transcription Factor 2
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Oligodendroglia / metabolism
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SOXE Transcription Factors / genetics*
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SOXE Transcription Factors / metabolism
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Spinal Cord / metabolism
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Spinal Cord / pathology
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Transcription Factors / genetics
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Zebrafish Proteins
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Fabp7 protein, mouse
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Fatty Acid-Binding Protein 7
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Fatty Acid-Binding Proteins
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Homeobox Protein Nkx-2.2
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Homeodomain Proteins
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NKX2-2 protein, human
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Nerve Tissue Proteins
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Nkx2-2 protein, mouse
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Nuclear Proteins
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Olig1 protein, mouse
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2
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SOXE Transcription Factors
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Transcription Factors
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Zebrafish Proteins
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myelin gene regulatory factor, mouse
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nkx2.2b protein, zebrafish
Grants and funding
The study was funded by the DFG (We 1326/11) and the Bavarian State Ministry of Education and Culture, Science and Arts in the framework of the Bavarian Research Network Induced Pluripotent Stem Cells (ForIPS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.