Defining the molecular identity and morphology of glia limitans superficialis astrocytes in vertebrates

Abstract

Astrocytes are a highly abundant glial cell type and perform critical homeostatic functions in the central nervous system. Like neurons, astrocytes have many discrete heterogeneous subtypes. The subtype identity and functions are, at least in part, associated with their anatomical location and can be highly restricted to strategically important anatomical domains. Here, we report that astrocytes forming the glia limitans superficialis, the outermost border of the brain and spinal cord, are a highly specialized astrocyte subtype and can be identified by a single marker: myocilin (Myoc). We show that glia limitans superficialis astrocytes cover the entire brain and spinal cord surface, exhibit an atypical morphology, and are evolutionarily conserved from zebrafish, rodents, and non-human primates to humans. Identification of this highly specialized astrocyte subtype will advance our understanding of CNS homeostasis and potentially be targeted for therapeutic intervention to combat peripheral inflammatory effects on the CNS.

Keywords: CP: Cell biology; CP: Neuroscience; astrocytes; glia limitans; meninges; scRNA-seq; spatial transcriptomics.