title: Elevated in vivo levels of a single transcription factor directly convert satellite glia into oligodendrocyte-like cells.
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.
authors: Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Matthias
authors: M
authors: Weider
authors: Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Amélie
authors: A
authors: Wegener
authors: Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Christian
authors: C
authors: Schmitt
authors: Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Melanie
authors: M
authors: Küspert
authors: Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Simone
authors: S
authors: Hillgärtner
authors: Experimentelle Biomedizin, Rudolf-Virchow-Zentrum, Universitätsklinikum Würzburg, Würzburg, Germany.
authors: Michael R
authors: MR
authors: Bösl
authors: ZMNH, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors: Irm
authors: I
authors: Hermans-Borgmeyer
authors: Institut du Cerveau et de la Moelle Epinière, ICM, Inserm U1127, Université Pierre et Marie Curie, Sorbonne Paris Cité, UMR-S1127, CNRS UMR 7225, Paris, France.
authors: Brahim
authors: B
authors: Nait-Oumesmar
authors: Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors: Michael
authors: M
authors: Wegner
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D004622:Embryo, Mammalian; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009457:Neuroglia; D009687:Nuclear Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D029961:Zebrafish Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D055757:SOXE Transcription Factors; D014157:Transcription Factors; D029961:Zebrafish Proteins; C086936:Fabp7 protein, mouse; C000715631:NKX2-2 protein, human; C000715627:Nkx2-2 protein, mouse; C494786:Olig1 protein, mouse; C512773:Olig2 protein, mouse; C571125:myelin gene regulatory factor, mouse; C000715630:nkx2.2b protein, zebrafish