Cytoplasmic translocation of Olig2 in adult glial progenitors marks the generation of reactive astrocytes following autoimmune inflammation.
The injury response in the brain involves complex interplay between neural and immune components. Following inflammatory insults to the adult CNS, formation of an astroglial scar often impedes functional repair. Glial progenitor cells expressing the nuclear transcription factor Olig2 possibly generate astrocytes in response to various types of injuries; however, the mechanisms underlying this differentiation are unclear. In a model of immune-mediated injury (MOG(35-55)-experimental autoimmune encephalomyelitis), we show that the conversion from progenitor to reactive astrocyte is marked by the translocation of Olig2 into the cytoplasm. Evidence of this process is found for months after disease initiation in the absence of new inflammatory infiltrates. A proportion of cells with cytoplasmic Olig2 was found to express NG2 or Nkx2.2, but only Nkx2.2 was occasionally retained by GFAP+ cells. We further show that differentiation to astrocytes is induced in glial progenitors in vitro through exposure to the pro-inflammatory cytokine IFN-gamma, but not to TNF-alpha. Together, these data ascribe a pivotal role to Olig2+ glial precursor cells in the adult CNS, linking autoimmune inflammation and glial scar formation.
Cassiani-Ingoni
Riccardo
R
Cellular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. cassianr@ninds.nih.gov
Coksaygan
Turhan
T
Xue
Haipeng
H
Reichert-Scrivner
Susan A
SA
Wiendl
Heinz
H
Rao
Mahendra S
MS
Magnus
Tim
T
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D000090322:Homeobox Protein Nkx-2.2; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D005904:Glial Fibrillary Acidic Protein; D000090322:Homeobox Protein Nkx-2.2; D007371:Interferon-gamma; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans; D012313:RNA; D014409:Tumor Necrosis Factor-alpha; D000099216:Chondroitin Sulfate Proteoglycan 4; C000715627:Nkx2-2 protein, mouse; C512773:Olig2 protein, mouse