Exploring hybrid networks made by neurons and progenitor cells

Neuronal stem cells (NSCs) and primitive progenitors (NPCs) play an essential role in homeostasis of the central nervous system (CNS). Due to their ability to differentiate into specific lineages, the possibility to manipulate these cell types could have a tremendous impact on future therapeutic approaches for brain or spinal cord injuries or degenerative diseases charachterized by neuronal loss. Thus, the study of the pathways involved in self-renewal and lineage-specific differentiation of stem cells is a pillar step to generate specific cell types required for clinical applications. We focused on fetal NPCs, a more committed subpopulation of NSCs, which are mostly cultured in vitro as neurospheres given their ability to proliferate and differentiate in all neuronal cell types. We tested wheter fNPCs could integrate among post-mitotic neurons and communicate with them by culturing them in co-culture in vitro system. This possibility was investigated by co-culturing fNPCS within hippocampal neurons, within dopaminergic neurons, obtained from substantia nigra compacta (SNc) and ventral tegmental area (VTA) and within cortical astrocytes. Our results suggest the capability of fNPCs to differently change their phenotype and cell development depending on the neural circuit they interact with. We further examined the main players responsible for such changes, including the soluble component released by different cell types and the firing properties of neurons.