title: Molecular identity of human outer radial glia during cortical development.
abstract: 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.
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: alex.pollen@gmail.com.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Pollen
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Nowakowski
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jiadong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Hanna
authors.initials: H
authors.lastname: Retallack
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandoval-Espinosa
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Cory R
authors.initials: CR
authors.lastname: Nicholas
authors.affiliation: Fluidigm Corporation, South San Francisco, CA 94080, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Shuga
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Siyuan John
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Oldham
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Diaz
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lim
authors.affiliation: Fluidigm Corporation, South San Francisco, CA 94080, USA.
authors.forename: Anne A
authors.initials: AA
authors.lastname: Leyrat
authors.affiliation: Fluidigm Corporation, South San Francisco, CA 94080, USA.
authors.forename: Jay A
authors.initials: JA
authors.lastname: West
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: kriegsteina@stemcell.ucsf.edu.
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Kriegstein
mesh_terms: D000818:Animals; D002453:Cell Cycle; D006801:Humans; D008251:Macaca; D051379:Mice; D019579:Neocortex / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D059010:Single-Cell Analysis; D055153:Stem Cell Niche
chemical_list: D050796:STAT3 Transcription Factor