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Developmental Origins of Astrocyte Heterogeneity: The Final Frontier of CNS Development

Astrocytes are the most abundant cell type in the central nervous system, have diverse physiological roles in both health and disease, and exhibit phenotypic heterogeneity. In spite of the overwhelming evidence that astrocytes are a diverse population, there has been relatively little consideration of their molecular heterogeneity. In this review, we will summarize what is known about the heterogeneity of astrocytes and outline challenges that have limited studies understanding their molecular diversity. Approaches that have sought to overcome these limitations will be discussed, with an emphasis on recent progress in the field of developmental gliogenesis, which has revealed that positional identity during embryogenesis is an organizing feature of astrocyte diversity. These recent findings, coupled with emerging technologies that allow for direct isolation of astrocyte populations, have led us to propose that approaches rooted in astrocyte development may be the key to unlocking this immense, untapped diversity.