Decoding the progeny of NG2 and GFAP progenitor cells.

Abstract

During cortical development, cell generation follow a sequential pattern in partially overlapping temporal waves. Firstly, neural progenitor cells (NPCs) derived from neuroepithelial cells divide symmetrically to expand their population pool, before their gradual transition into radial glia (RG) cells. RG cells initially undergo symmetric cell divisions and later asymmetric RG division produce neurons first, then astrocytes and at later stages oligodendrocytes. Recent studies support the notion that RG cells might be heterogeneous regarding their differentiation and fate potential. Another remarkable cell type, which could act as precursor cells, are NG2-cells. In vivo cell fate analyses indicate that NG2-cells are oligodendrocyte precursor cells (OPCs) but fate-mapping analysis, in different transgenic mice lines, also revealed different degrees of differentiation and maturation properties of NG2 cells depending on brain areas. In addition, some studies suggest that in response to brain injury reactive astrocytes arise from endogenous progenitors located in the adult brain parenchyma like NG2 cells. Thus, such diversity implies that those cells conform a heterogeneous population composed by different subpopulations devoted to distinct functions. Then, most NG2-cells lineage is unknown and has not been explored to decode whether the NG2-cells is a homogeneous cell population that displays different properties depending on environmental influences or is an intrinsically heterogeneous cell. In order to decipher the cell progeny of early neural progenitors expressing either GFAP or NG2, we targeted SVZ progenitors. To this end, we exchanged the CMV promoter in the piggyback transposase by the GFAP (GFAP-hyPBase) or the NG2 (NG2-hyPBase) promoters to produce specific labeling of progenitor cells that are expressing GFAP or NG2 genes at the time of electroporation. These new transposases also recognize the terminal repeats of UbC-StarTrack plasmids to guarantee the permanent labeling of neural cells. Then, after in vivo electroporation of the Ubc-StarTrack mixture along with the different transposase, we analyzed their cell progeny in adult brain mouse allowing to distinguish different cell subpopulations between GFAP progenitors or NG2 progenitors. Our findings provide fundamental aspects of the lineage heterogeneity and cell fate determination of different and specific progenitor cells