Astrocyte Differentiation of Human Pluripotent Stem Cells: New Tools for Neurological Disorder Research

Astrocytes have a central role in brain development and function, and so have gained
increasing attention over the past two decades. Consequently, our knowledge about
their origin, differentiation and function has increased significantly, with new research
showing that astrocytes cultured alone or co-cultured with neurons have the potential
to improve our understanding of various central nervous system diseases, such as
amyotrophic lateral sclerosis, Alzheimer’s disease, or Alexander disease. The generation
of astrocytes derived from pluripotent stem cells (PSCs) opens up a new area for
studying neurologic diseases in vitro; these models could be exploited to identify
and validate potential drugs by detecting adverse effects in the early stages of drug
development. However, as it is now known that a range of astrocyte populations exist
in the brain, it will be important in vitro to develop standardized protocols for the in vitro
generation of astrocyte subsets with defined maturity status and phenotypic properties.
This will then open new possibilities for co-cultures with neurons and the generation
of neural organoids for research purposes. The aim of this review article is to compare
and summarize the currently available protocols and their strategies to generate human
astrocytes from PSCs. Furthermore, we discuss the potential role of human-induced
PSCs derived astrocytes in disease modeling.