Variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates

Author:

Micali Nicola,Kim Suel-Kee,Diaz-Bustamante Marcelo,Stein-O’Brien Genevieve,Seo Seungmae,Shin Joo-Heon,Rash Brian G.,Ma Shaojie,Wang Yanhong,Olivares Nicolas A.,Arellano Jon,Maynard Kristen R.,Fertig Elana J.,Cross Alan J.,Burli Roland,Brandon Nicholas J.,Weinberger Daniel R.,Chenoweth Joshua G.,Hoeppner Daniel J.,Sestan Nenad,Rakic Pasko,Colantuoni Carlo,McKay Ronald D.

Abstract

SUMMARYBetter understanding the progression of neural stem cells (NSCs) in the developing 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 and human in vitro NSCs to model the generation of cortical neuronal fates. We show that conserved signaling mechanisms regulate the acute transition from proliferative NSCs to committed glutamatergic excitatory neurons. As human telencephalic NSCs developed from pluripotency in vitro, they first transitioned through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines varied in these early patterning states leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analysis of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon.

Publisher

Cold Spring Harbor Laboratory

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