Elevated in vivo levels of a single transcription factor directly convert satellite glia into oligodendrocyte-like cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-144123
  • 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 systemOligodendrocytes 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.show moreshow less

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Metadaten
Author: Matthias Weider, Amélie Wegener, Christian Schmitt, Melanie Küspert, Simone Hillgärtner, Michael R. Bösl, Irm Hermans-Borgmeyer, Brahim Nait-Oumesmar, Michael Wegner
URN:urn:nbn:de:bvb:20-opus-144123
Document Type:Journal article
Faculties:Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):PLoS Genetics
Year of Completion:2015
Volume:11
Issue:2
Pagenumber:e1005008
Source:PLoS Genetics 11(2): e1005008 (2015). DOI: 10.1371/journal. pgen.1005008
DOI:https://doi.org/10.1371/journal.pgen.1005008
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Hirschsprung disease; Olig2; boundary cap; differentiation; expression; factor Sox10; mouse model; peripheral nervous system; spinal-cord; stem cells
Release Date:2018/06/14
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International