Molecular Identity of Human Outer Radial Glia During Cortical Development

By Alex A. Pollen, T. Nowakowski, Jiadong Chen, H. Retallack, Carmen Sandoval-Espinosa, Cory R. Nicholas, Joe Shuga, S. Liu, Michael C. Oldham, A. Diaz and 4 more. Cell, 2015

795 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/db4e28c6ab7f342246be1fd7e1d774f77aab83b0

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Citations in the corpus

Cell diversity and network dynamics in photosensitive human brain organoids (2017, methodology): “Subclusters 16–23 were enriched for human radial glia markers 22 , whereas subcluster 4 was distinguished by the expression of canonical genes of intermediate progenitors, including EOMES and ELAVL4 .”
hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023, methodology): “Radial glia, which share transcriptomic similarities with mature astrocytes, are progenitor cells that give rise to numerous distinct cell fates, including neuronal cells, astrocytes, oligodendrocytes, and ependymal cells.(34,35) To model this developmental process, we applied Monocle3(36) pseudotim”
Multi-omics single-cell data integration and regulatory inference with graph-linked embedding (2022, background): “Further inspection revealed that canonical radial glial markers such as PAX6 , HES1 and HOPX 47,48 were actively transcribed in this cluster, both in the RNA and ATAC domain (Supplementary Fig.”
Brain Region-specific Organoids using Mini-bioreactors for Modeling ZIKV Exposure (2016, positive): “Recent studies have identified markers preferentially expressed by oRGCs in the developing human cortex, including HOPX, FAM107A and PTPRZ1 (Pollen et al., 2015; Thomsen et al., 2015).”
Human cerebral organoids recapitulate gene expression programs of fetal neocortex development (2015, methodology): “A study published while our manuscript was in review used scRNA-seq to survey the human cerebral cortex at gestational week 16–18 and reported the identification of a bRG (aka oRG) gene expression signature (29).”