title: Human pluripotent stem cell-derived radial glia recapitulate developmental events and provide real-time access to cortical neurons and astrocytes.
abstract: Studies of human cerebral cortex development are limited by difficulties in accessing and manipulating human neural tissue at specific development stages. We have derived human radial glia (hRG), which are responsible for most cerebral cortex neurogenesis, from human pluripotent stem cells. These hRG display the hallmark morphological, cellular, and molecular features of radial glia in vitro. They can be passaged and generate layer-specific subtypes of cortical neurons in a temporal and passage-dependent fashion. In later passages, they adopt a distinct progenitor phenotype that gives rise to cortical astrocytes and GABAergic interneurons. These hRG are also capable of following developmental cues to engraft, differentiate, migrate, and integrate into the embryonic mouse cortex when injected into E14 lateral ventricles. Moreover, hRG-derived cells can be cryopreserved at specific stages and retain their stage-specific phenotypes and competence when revived. Our study demonstrates that cultured hRG maintain a cell-intrinsic clock that regulates the progressive generation of stage-specific neuronal and glial subtypes. It also describes an easily accessible cell source for studying hRG lineage specification and progression and an on-demand supply of specific cortical neuron subtypes and astrocytes.
authors.affiliation: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA lishuduan2011@u.northwestern.edu.
authors.forename: Lishu
authors.initials: L
authors.lastname: Duan
authors.affiliation: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Chian-Yu
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Liuliu
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Kessler
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics*; D002540:Cerebral Cortex / Q000166:cytology*; D063928:Ependymoglial Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism
keywords: Astrocytes; Cortical interneuron; Cortical neuron; Human embryonic stem cells; Human iPS cells; Radial glia
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