NG2 cells generate both oligodendrocytes and gray matter astrocytes

Abstract

*NG2 glia constitute a fourth major glial cell type in the mammalian central nervous system (CNS) that is distinct from other cell types. Although circumstantial evidence suggests that some NG2 glia differentiate into oligodendrocytes, their in vivo fate has not been directly examined. We have used the bacterial artificial chromosome (BAC) modification technique to generate transgenic mice that express DsRed or Cre specifically in NG2-expressing (NG2+) cells. In NG2DsRedBAC transgenic mice, DsRed was expressed specifically in NG2+ cells throughout the postnatal CNS. When the differentiation potential of NG2+ cells in vitro was examined using DsRed+NG2+ cells purified from perinatal transgenic brains, the majority of the cells either remained as NG2+ cells or differentiated into oligodendrocytes. In addition, DsRed+NG2+ cells also differentiated into astrocytes. The in vivo fate of NG2 glia was examined in mice that were double transgenic for NG2creBAC and the Cre reporter Z/EG. In the double transgenic mice, the Cre reporter EGFP was detected in myelinating oligodendrocytes and in a subpopulation of protoplasmic astrocytes in the gray matter of ventrolateral forebrain but not in fibrous astrocytes of white matter. These observations suggest that NG2+ cells are precursors of oligodendrocytes and some protoplasmic astrocytes in gray matter.

Progeny of Olig2-Expressing Progenitors in the Gray and White Matter of the Adult Mouse Cerebral Cortex

“…This is in pronounced contrast to the multitude of lineages observed to arise from this progenitor pool during development using even the very same mouse line Masahira et al, 2006;Miyoshi et al, 2007;Ono et al, 2008) or the NG2::CreERTM T2 line (Zhu et al, 2008). Importantly, during development, the different cell types arise from distinct sets of Olig2 ϩ progenitors (e.g., Olig2 ϩ cells that generate motoneurons do not share their lineage with those that generate oligodendrocytes) (Mukouyama et al, 2006;Wu et al, 2006).…”

“…Interestingly, Olig2 is also required for the specification of NG2 ϩ cells (Ligon et al, 2006b). Similar to Olig2, NG2 is also expressed in progenitors of various lineages, including oligodendrocytes and astrocytes during development (Cai et al, 2007;Zhu et al, 2008;Ono et al, 2008), as well as multipotent progenitors in the postnatal brain (Belachew et al, 2003;Aguirre et al, 2004) and possibly even neuronal progenitors in the adult cerebral cortex (Dawson et al, 2000;Dayer et al, 2005;Tamura et al, 2007).…”

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

“…In the G93A mSOD1 transgenic mouse, activation of astrocytes occurs concomitantly with a decrease in motor neurons [75,82,83]. Although astrocyte numbers increase with disease progression, astrocytes do not proliferate like microglia, but may be derived from ependymal cells lining the central canal of the spinal cord or oligodendrocyte precursor cells [24,[84][85][86][87][88].…”

Strategies for immunohistochemical protein localization using antibodies: What did we learn from neurotransmitter transporters in glial cells and neurons

“…This offers new opportunities for studies of cell progeny (e.g. Malatesta et al, 2003;Zhu et al, 2008;Platel et al, 2009;Huang et al, 2014), visualization of astrocytes and astrogliosis in living brain tissue (Nolte et al, 2001;Weimer et al, 2008;Tang et al, 2009) and other dynamic interactions which are hard to study immunocytochemically (e.g. Reichenbach et al, 2010;Young et al, 2010;Herzog et al, 2011).…”