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

Weider M, Wegener A, Schmitt C, Küspert M, Hillgärtner S, Bösl MR, Hermans-Borgmeyer I, Nait-Oumesmar B, Wegner M - PLoS Genet. (2015)

Bottom Line: These rarely studied and poorly characterized satellite glia did not go through a classic oligodendrocyte precursor cell stage.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.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

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.

Show MeSH

Related in: MedlinePlus

Olig2 overexpression does not generate oligodendrocyte-like cells in DRG.(A) Spinal cord (SC), DRG and peripheral nerves (N) are schematically shown at E18.5. (B-I) IHC and ISH were carried out on transverse sections (thoracic level) of wildtype (Wt) and 2TetOlig2 embryos at E18.5 with antibodies directed against Olig2 (B, F) and riboprobes against Mbp (C, G), Plp1 (D, H) and Myrf (E, I) and. Pictures were taken from the boxed DRG area. Size bars: 50 μm in B (valid for B-I).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4334169&req=5

pgen.1005008.g011: Olig2 overexpression does not generate oligodendrocyte-like cells in DRG.(A) Spinal cord (SC), DRG and peripheral nerves (N) are schematically shown at E18.5. (B-I) IHC and ISH were carried out on transverse sections (thoracic level) of wildtype (Wt) and 2TetOlig2 embryos at E18.5 with antibodies directed against Olig2 (B, F) and riboprobes against Mbp (C, G), Plp1 (D, H) and Myrf (E, I) and. Pictures were taken from the boxed DRG area. Size bars: 50 μm in B (valid for B-I).

Mentions: Finally we asked whether the presence of Olig2 in DRG glia is sufficient to induce oligodendrocyte-like cells. For that purpose we exchanged the TetSox10 transgene by an analogously constructed TetOlig2 transgene [27] and probed the DRG of 2TetOlig2 mice at E18.5 for the expression of the myelin genes Mbp and Plp1 and Myrf as a marker for differentiating oligodendrocytes. Unlike 2TetSox10 mice, 2TetOlig2 mice were indistinguishable from the wildtype in that oligodendrocyte markers were not expressed (compare Fig. 11C-E, G-I to Fig. 2C-E, G-I). Therefore Olig2 cannot convert satellite glia into oligodendrocyte-like cells.


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

Weider M, Wegener A, Schmitt C, Küspert M, Hillgärtner S, Bösl MR, Hermans-Borgmeyer I, Nait-Oumesmar B, Wegner M - PLoS Genet. (2015)

Olig2 overexpression does not generate oligodendrocyte-like cells in DRG.(A) Spinal cord (SC), DRG and peripheral nerves (N) are schematically shown at E18.5. (B-I) IHC and ISH were carried out on transverse sections (thoracic level) of wildtype (Wt) and 2TetOlig2 embryos at E18.5 with antibodies directed against Olig2 (B, F) and riboprobes against Mbp (C, G), Plp1 (D, H) and Myrf (E, I) and. Pictures were taken from the boxed DRG area. Size bars: 50 μm in B (valid for B-I).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4334169&req=5

pgen.1005008.g011: Olig2 overexpression does not generate oligodendrocyte-like cells in DRG.(A) Spinal cord (SC), DRG and peripheral nerves (N) are schematically shown at E18.5. (B-I) IHC and ISH were carried out on transverse sections (thoracic level) of wildtype (Wt) and 2TetOlig2 embryos at E18.5 with antibodies directed against Olig2 (B, F) and riboprobes against Mbp (C, G), Plp1 (D, H) and Myrf (E, I) and. Pictures were taken from the boxed DRG area. Size bars: 50 μm in B (valid for B-I).
Mentions: Finally we asked whether the presence of Olig2 in DRG glia is sufficient to induce oligodendrocyte-like cells. For that purpose we exchanged the TetSox10 transgene by an analogously constructed TetOlig2 transgene [27] and probed the DRG of 2TetOlig2 mice at E18.5 for the expression of the myelin genes Mbp and Plp1 and Myrf as a marker for differentiating oligodendrocytes. Unlike 2TetSox10 mice, 2TetOlig2 mice were indistinguishable from the wildtype in that oligodendrocyte markers were not expressed (compare Fig. 11C-E, G-I to Fig. 2C-E, G-I). Therefore Olig2 cannot convert satellite glia into oligodendrocyte-like cells.

Bottom Line: These rarely studied and poorly characterized satellite glia did not go through a classic oligodendrocyte precursor cell stage.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.

View Article: PubMed Central - PubMed

Affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

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.

Show MeSH
Related in: MedlinePlus