Derived Primate-Specific Astroglia Reveal Brain Disorder Traits

Abstract

The biological functions of primate-specific astroglia, interlaminar astrocytes (IAs), remain enigmatic due to the lack of access to experimental materials, especially in humans. Here, we develop a protocol for the derivation of IAs from healthy normal and schizophrenia patient (SCZ)-specific human pluripotent stem cells. We find that IAs possess a functional profile which is distinct from that of protoplasmic astrocytes, particularly in synapse-associated functions such as neuroactive ligand-receptor interactions, calcium signaling, and long-term potentiation. These synaptic functions are further corroborated by our findings that IAs respond to glutamate, which mediates Ca2+ signaling and in turn leads to the release of gliotransmitters to interact with neurons and astrocytes. We further show that SCZ IAs shift their functional characteristic from synaptic signaling to Matrix-associated functions, with a notable impairment in the levels of gliotransmitters. We anticipate that these findings will prompt more penetrating investigations into the role of IAs in glia biology and brain disorders.