Determining the effect of inflammation on the differentiation of neural stem cells into astrocytes
Neural stem cells (NSCs) can self-renew and give rise to different cell types in the embryonic and adult nervous systems. As such, they are pivotal to our understanding of specification within the nervous system and for deploying NSCs as a tool in regenerative medicine. The contribution of genetic and epigenetic mechanisms in the maintenance or differentiation of NSCs are currently emerging. Several studies have nicely demonstrated the importance of the underlying epigenetic mechanisms, including DNA methylation and histone modifications, along cell lineage specification and progressive NSCs fate restriction. For instance, it has been shown that the loss of bivalency underlies developmental transitions at several promoters in line with their increasing developmental restriction from pluripotent embryonic stem cells through multipotent NSCs to committed GABAergic interneurons.
Under neuroinflammatory conditions, the release of mediators, including cytokines and free radicals, affects intrinsic NSC properties and their ability to differentiate into specific cell lineages. In this context, little is known about the epigenetic and transcriptional changes that underlie NSCs differentiation into astrocytes under inflammatory conditions. Due to the multiple roles that astrocytes carry out in the developing and adult brain, we hypothesize that defects during their differentiation could affect the underlying neuronal network, thus giving rise to several neurological disorders.
Therefore, in the present project, we propose to investigate the effect of inflammatory or infectious events on the differentiation of NSCs into astrocytes by profiling their epigenetic and transcriptional programs.
This project is supported by the University of Luxembourg (IRP ASTROSYS).