Abstract
Accumulating studies demonstrate the morphological and functional diversity of astrocytes, a subtype of glial cells in the central nervous system. Animal models are instrumental in advancing our understanding of the role of astrocytes in brain development and their contribution to neurological disease; however, substantial interspecies differences exist between rodent and human astrocytes, underscoring the importance of studying human astrocytes. Human pluripotent stem cell differentiation approaches allow the study of patient-specific astrocytes in the etiology of neurological disorders. In this review, we summarize the structural and functional properties of astrocytes, including the unique features of human astrocytes; demonstrate the necessity of the stem cell platform; and discuss how this platform has been applied to the research of neurodevelopmental and neuropsychiatric diseases.
Highlights
IntroductionSensory, and social impairments associated with neurodevelopmental disorders, including Down syndrome, Rett syndrome, and schizophrenia, negatively impact the quality of life of affected individuals and their families
Astrocytes Derived fromCognitive, sensory, and social impairments associated with neurodevelopmental disorders, including Down syndrome, Rett syndrome, and schizophrenia, negatively impact the quality of life of affected individuals and their families
Astrocytes participate in long-term memory consolidation and allocation [83,84]. These results suggest the significance of astrocytes in synaptic refinement and learning and memory, implicating the involvement of astrocytes in the pathology of several neurodevelopmental and neuropsychiatric diseases
Summary
Sensory, and social impairments associated with neurodevelopmental disorders, including Down syndrome, Rett syndrome, and schizophrenia, negatively impact the quality of life of affected individuals and their families. The brain, as the etiological site, is the most complex organ and remains incompletely studied These disorders have relatively high heterogeneity in phenotypes and complexity in mechanisms, making it challenging to understand the pathogenesis and identify therapeutic targets. Impairments in the morphology and function of astrocytes could exert a profound influence on the homeostasis of the brain, contributing to cellular mechanisms underlying the cognitive, behavioral, and affective impairments in neurodevelopmental and neuropsychiatric disorders. Animal models, such as drosophila, zebrafish, and rodents, have been developed over decades to study the molecular and genetic mechanisms involved in the etiology. In this review, we will discuss the recent accomplishments in the differentiation of hiPSCs to astrocytes and the application of these cells to the study of neurodevelopmental and neuropsychiatric disorders, highlighting the gap in knowledge filled by human astrocyte models as well as current limitations and opportunities of these models
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