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Human cortical neural stem cells generate regional organizer states in vitro before committing to excitatory neuronal fates
Brian G. Rash,
Nicolas A. Olivares,
Kristen R Maynard,
Elana J. Fertig,
Alan J. Cross,
Nicholas J Brandon,
Daniel R Weinberger,
Joshua G Chenoweth,
Daniel J. Hoeppner,
Ronald D McKay
Posted 15 Mar 2019
bioRxiv DOI: 10.1101/577544
Posted 15 Mar 2019
Better understanding of the mechanisms underlying the developmental progression of neural stem cells (NSCs) in the cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here we used RNA-sequencing, cell imaging and lineage tracing of mouse, macaque and human neurogenesis, along with single-cell RNA-sequencing and immuno-labeling to explore how cortical glutamatergic excitatory neurons are generated in vitro and in vivo. This analysis revealed that conserved signaling mechanisms regulate glutamatergic neurogenesis among the three species. We then show that as human telencephalic NSCs develop in vitro, they first generate the organizer states that spatially pattern the cortex before progressing to excitatory neuronal fates. This developmental progression of human NSCs in vitro opens to systematic analysis key aspects of human-specific area patterning during cortical neurogenesis.
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