Cell Progeny and Cell Potential Of NG2-progenitors

Laburpena

The assembly of the brain from a pool of Neural Progenitor Cells (NPCs) is an immensely complex process. During mammalian brain development, Radial Glial Progenitors (RGPs), derived from Neuroepithelial cells (NE), undergo asymmetric divisions after symmetric divisions to generate, in partially overlapping temporal waves, first neurons, then astrocytes and last oligodendrocytes and NG2-glia. It is now clear that few cortical progenitors, at early embryonic stages, appear to be lineage multipotent, and recent studies reinforce the idea that NPCs conform to a heterogeneous population. We hypothesize that embryonic NG2+ cells could act as progenitors, given the potential of adult NG2-glia to generate mainly oligodendrocytes, but also astrocytes or even neurons in some regions or specific conditions. In this thesis, our objective is to decipher the progeny and the potential of NG2-progenitors during mouse brain development and to compare them with RGPs. To investigate this, we used modifications of the lineage tracking method StarTrack to target single NG2-progenitors and RGPs with a stable and heritable label. We analyzed and compared the cell progeny, cell potential and immunohistochemical profile of NG2-progenitors and RGPs at different stages. Additionally, we performed a preliminary assessment of the cell dynamics and transcriptomic profile of both NPCs. Our results reveal that pallial NG2-progenitors generate both neurons and glia, changing their fate throughout brain development. Furthermore, they are a diverse population, as clonal size, rostro-caudal dispersion and cortical distribution of their progeny were not homogenous. However, we could not determine if RGPs and NG2-progenitors are different progenitors or transitional stages of the same cell population. Further analyses combining StarTrack and RNA sequencing could help to clarify this issue. Overall, this thesis contributes to our understanding of the complex process of brain development and supports new evidence of NG2-progenitor potential and neural progenitor cell heterogeneity