Morphological heterogeneity of human astrocytes in a cerebral organoid

Abstract

Astrocytes are a type of glial cell in the central nervous system responsible for modulating synaptic transmissions, tissue repair, maintaining homeostasis, and are therefore implicated in many neurological diseases. Historically, cortical astrocytes were assumed to be a homogeneous population; however, it has recently been demonstrated that there is both morphological and transcriptome heterogeneity between cortical layers, implying diverse functional capacities and responsibilities. Human astrocytes are also more structurally complex, larger, and have unique subtypes in comparison to the commonly studied rodent astrocytes. As access to human cortical tissue is sparse, emerging cerebral organoids derived from human stem cells have become a popular in vitro model for studying the human cortex. Here we show that cerebral organoids recapitulate morphologically distinct protoplasmic, fibrous, and interlaminar astrocyte subtypes, and their morphologies are reconstructed and quantitatively characterized. It was also found that protoplasmic astrocytes in cerebral organoids are more structurally complex than those found in rodents. Establishing astrocyte morphologies in a cerebral organoid model is an important step in understanding the diverse functions of astrocytes in a human context.