ACSA-2 and GLAST classify subpopulations of neurogenic and glial restricted cerebellar precursors

ABSTRACT: Neurogenic astroglia-like cells of the prospective white matter (PWM) generate interneurons and astroglia during cerebellar development. However, the characterization of PWM subpopulations is still insufficient. Here we show that ACSA-2 (Astrocyte Cell Surface Antigen-2) is an intrinsic marker of astrocyte-committed precursors. In the developing cerebellum, the ontogeny of ACSA-2+ astrocytes revealed this epitope to be exclusively expressed by PWM cells. By contrast, in the adult brain, ACSA-2 is observed on parenchymal astrocytes, fibrous astrocytes of the white matter and at low level on Bergmann glia. In combination with GLAST, a marker for astroglia-like progenitors, we addressed the characteristics of neurogenic (ACSA-2-/GLAST+) and astrocyte-committed (ACSA-2+/GLAST+) precursors using transcriptomics and cell transplantation assays. Gene expression analyses identified major differences in genes related to the maturation status of astrocytes, their potential to generate interneurons and genes required for Bergmann glia specification. Transplantation assays further confirmed a divergent differentiation potential: ACSA-2+/GLAST+ cells, on the one side, differentiate into astrocytes and oligodendrocytes but not into Bergmann glia or neurons when transplanted into the neonatal cerebellum. On the other side, ACSA-2-/GLAST+ progenitors were able to generate interneurons and all the glial phenotypes. Moreover, ACSA-2-/GLAST+ progenitors even maintained the neurogenic potential when transplanted into the adult cerebellum. In conclusion, this work reports about ACSA-2, a marker for glial-restricted precursors of the PWM that in combination with GLAST enables for the discrimination and isolation of neurogenic and astrocyte-committed progenitors of the neonatal cerebellum.

ORGANISM(S): Mus musculus

PROVIDER: GSE117886 | GEO | 2021/09/29

REPOSITORIES: GEO