Deciphering neural heterogeneity through startrack cell lineage analyses

Résumé

The diversity and complexity of the nervous system are some of the most relevant topics in Neurosciences. Over the past few decades, there has been an increasing interest in the heterogeneity of neural cells. Neural progenitor cells (NPCs) give rise to distinct cell types at different embryonic and adult stages increasing the neural diversity in the brain. Understanding the balance between proliferation and differentiation of progenitor cells to give rise to a functional adult nervous system is a challenging process in the Developmental field of research. In our lab, we focus on the study of the heterogeneity of NPCs to unravel the diversity of the neural lineages. StarTrack, a multicolor genetic lineage tracing system, allowed targeting progenitor cells to track the cell type and location of the adult cell-derived progeny, as well as their lineage relationships. This Thesis project aimed to permanently label the individual progenitor cells and their progeny according to the identity of the progenitor cells by designing different StarTrack approaches. Specific NPCs are determined to generate different neural cells (namely astrocytes, oligodendrocytes, NG2-cells and neurons), located in the gray and white matter, related to the NPC identity at different regions of the telencephalon. Moreover, the clonal analysis of the postnatal NPCs revealed a committed capacity to develop into different lineages focused on glial cells. Our findings provide fundamental aspects of progenitor potential, cell fate determination, and heterogeneity of NPCs and their progeny, that might help gaining new insights into their behavior, complexity, and functionality within the system.