Specified glial precursors then migrate from the progenitor zones to the brain parenchyma where they proliferate and differentiate during early postnatal stages 1, 2. First, a ‘gliogenic switch’ enables NSCs to progress from neurogenesis to the generation of astrocytes and oligodendrocytes. Astrocytes are generated from neural stem cells (NSCs) during late embryonic and early postnatal stages. Therefore, extrinsic signals orchestrate the expression of multiple intrinsic regulators, which in turn induce in a modular manner the transcriptional and chromatin changes underlying astrocyte maturation.Īstrocytes are the most abundant glial cells in the mammalian central nervous system and they serve essential functions in brain development and homoeostasis.
Culturing astrocytes in a three-dimensional matrix containing FGF2 induces expression of Rorb, Dbx2 and Lhx2 and improves astrocyte maturity based on transcriptional and chromatin profiles. Forced expression of these factors in vitro induces distinct sets of mature astrocyte-specific transcripts. Investigating astrocyte maturation in a cell culture model revealed that in vitro-differentiated astrocytes lack expression of many mature astrocyte-specific genes, including genes for the transcription factors Rorb, Dbx2, Lhx2 and Fezf2. Here we identify extensive transcriptional changes that occur during murine astrocyte maturation in vivo that are accompanied by chromatin remodelling at enhancer elements. Astrocytes have essential functions in brain homeostasis that are established late in differentiation, but the mechanisms underlying the functional maturation of astrocytes are not well understood.