Abstract
Determining the origin of different glial subtypes is crucial to understand glial heterogeneity, and to enhance our knowledge of glial and progenitor cell behavior in embryos and adults. NG2-glia are homogenously distributed in a grid-like manner in both, gray and white matter of the adult brain. While some NG2-glia in the CNS are responsible for the generation of mature oligodendrocytes (OPCs), most of them do not differentiate and they can proliferate outside of adult neurogenic niches. Thus, NG2-glia constitute a heterogeneous population containing different subpopulations with distinct functions. We hypothesized that their diversity emerges from specific progenitors during development, as occurs with other glial cell subtypes. To specifically target NG2-pallial progenitors and to define the NG2-glia lineage, as well as the NG2-progenitor potential, we designed two new StarTrack strategies using the NG2 promoter. These approaches label NG2 expressing progenitor cells, permitting the cell fates of these NG2 progenitors to be tracked in vivo. StarTrack labelled cells producing different neural phenotypes in different regions depending on the age targeted, and the strategy selected. This specific genetic targeting of neural progenitors in vivo has provided new data on the heterogeneous pool of NG2 progenitors at both embryonic and postnatal ages.
Highlights
NG2-glia are the main proliferative neural cells in the adult brain, representing about 5% of all the CNS cells[1,2,3]
NG2-glia give rise to cells of the oligodendrocyte lineage and to a few astrocytes[10,11,12]. These cells generate mature oligodendrocytes, most of them do not differentiate into oligodendrocytes in the adult CNS13,14, rather they remain in a “progenitor” state
NG2-glia have the potential to generate a variety of cell types like astrocytes and neurons, both in vitro and in vivo, and at either postnatal or adult stages[17,18,19,20], the latter is still not fully clear[3,5,11,21,22]
Summary
NG2-glia are the main proliferative neural cells in the adult brain, representing about 5% of all the CNS cells[1,2,3]. What is known is that they increase in number following traumatic insults) and that they contribute to the formation of glial scars, suggesting they help limit neurodegeneration[1,16] It is not clear whether these features are common to all NG2-glia cells or if there are different subpopulations that fulfil specific functions. NG2-glia have the potential to generate a variety of cell types like astrocytes and neurons, both in vitro and in vivo, and at either postnatal or adult stages[17,18,19,20], the latter is still not fully clear[3,5,11,21,22] This diversity could reflect the potential heterogeneity within the NG2-glia population based on their localization or on developmental factors that condition their activity and progeny[23]. Using new StarTrack strategies, directed to target NG2-progenitors at different developmental ages, we provide some answers to the cell fate and to the heterogeneity of this population of cells
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