Cell
Volume 163, Issue 1, 24 September 2015, Pages 55-67
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Article
Molecular Identity of Human Outer Radial Glia during Cortical Development

https://doi.org/10.1016/j.cell.2015.09.004Get rights and content
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Highlights

  • oRG and vRG cells represent molecularly distinct subpopulations of human radial glia

  • oRG transcriptional state first emerges in VZ during early cortical development

  • Single oRG cells generate hundreds of daughter cells of diverse types

  • Molecular profile suggests that oRG cells sustain proliferative niche in primate OSVZ

Summary

Radial glia, the neural stem cells of the neocortex, are located in two niches: the ventricular zone and outer subventricular zone. Although outer subventricular zone radial glia may generate the majority of human cortical neurons, their molecular features remain elusive. By analyzing gene expression across single cells, we find that outer radial glia preferentially express genes related to extracellular matrix formation, migration, and stemness, including TNC, PTPRZ1, FAM107A, HOPX, and LIFR. Using dynamic imaging, immunostaining, and clonal analysis, we relate these molecular features to distinctive behaviors of outer radial glia, demonstrate the necessity of STAT3 signaling for their cell cycle progression, and establish their extensive proliferative potential. These results suggest that outer radial glia directly support the subventricular niche through local production of growth factors, potentiation of growth factor signals by extracellular matrix proteins, and activation of self-renewal pathways, thereby enabling the developmental and evolutionary expansion of the human neocortex.

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Present address: Neurona Therapeutics, South San Francisco, CA 94080, USA