Human pluripotent stem cell-derived radial glia recapitulate developmental events and provide real-time access to cortical neurons and astrocytes

Lishu Duan*, Chian Yu Peng, Liuliu Pan, John A. Kessler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 andcompetence when revived. Our study demonstrates that cultured hRG maintainacell-intrinsic clock that regulates the progressive generation of stage-specific neuronal and glial subtypes. It also describesan easily accessible cell source for studying hRG lineage specification and progression and an on-demand supply of specific cortical neuron sub-types and astrocytes.

Original languageEnglish (US)
Pages (from-to)437-447
Number of pages11
JournalStem Cells Translational Medicine
Volume4
Issue number5
DOIs
StatePublished - 2015

Keywords

  • Astrocytes
  • Cortical interneuron
  • Cortical neuron
  • Human embryonic stem cells
  • Human iPS cells
  • Radial glia

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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