title: Astrocytes and oligodendrocytes can be generated from NG2+ progenitors after acute brain injury: intracellular localization of oligodendrocyte transcription factor 2 is associated with their fate choice.
abstract: Brain injury induces gliosis and scar formation; its principal cell types are mainly astrocytes and some oligodendrocytes. The origin of the astrocytes and oligodendrocytes in the scar remains unclear together with the underlying mechanism of their fate choice. We examined the response of oligodendrocyte transcription factor (Olig)2(+) glial progenitors to acute brain injury. Both focal cortical (mechanical or excitotoxic) and systemic (kainic acid-induced seizure or lipopolysaccharide-induced inflammation) injury caused cytoplasmic translocation of Olig2 (Olig2(TL)) exclusively in affected brain regions as early as 2 h after injury in two-thirds of Olig2(+) cells. Many of the proliferating Olig2(+) cells reacting to injury co-expressed chondroitin sulphate proteoglycan neuron/glia antigen 2 (NG2). Using 5-bromodeoxyuridine (BrdU) tracing protocols, proliferating Olig2(TL)GFAP(+)BrdU(+) cells were observed from 2 days post-lesion (dpl). Immature oligodendrocytes were also seen from 2 dpl and all of them retained Olig2 in the nucleus (Olig2(Nuc)). From 5 dpl Olig2(TL)NG2(+)GFAP(+) cells were observed in the wound and some of them were proliferative. From 5 dpl NG2(+)RIP(+) cells were also seen, all of which were Olig2(Nuc) and some of which were also BrdU(+). Our results suggest that, in response to brain injury, NG2(+) progenitors may generate a subpopulation of astrocytes in addition to oligodendrocytes and their fate choice was associated with Olig2(TL) or Olig2(Nuc). However, the NG2(+)GFAP(+) phenotype was only seen within a limited time window (5-8 dpl) when up to 20% of glial fibrillary acidic protein (GFAP) cells co-expressed NG2. We also observed Olig2(TL)GFAP(+) cells that appeared after injury and before the NG2(+)GFAP(+) phenotype. This suggests that not all astrocytes are derived from an NG2(+) population.
authors.affiliation: Department of Clinical Neurosciences, Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, UK.
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Zhao
authors.forename: Ruma
authors.initials: R
authors.lastname: Raha-Chowdhury
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism*; D001253:Astrocytes / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001930:Brain Injuries / Q000139:chemically induced / Q000503:physiopathology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced / Q000503:physiopathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007608:Kainic Acid; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013234:Stem Cells / Q000502:physiology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D005904:Glial Fibrillary Acidic Protein; D007608:Kainic Acid; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C512773:Olig2 protein, mouse; C522729:Olig2 protein, rat