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Variation of human neural stem cells generating organizer statesin vitrobefore committing to cortical excitatory or inhibitory neuronal fates
- Source :
- Cell reports, Cell Reports, Vol 31, Iss 5, Pp-(2020)
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- SUMMARY Better understanding of 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 use RNA sequencing, cell imaging, and lineage tracing of mouse and human in vitro NSCs and monkey brain sections 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 develop from pluripotency in vitro, they transition through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines vary in these early patterning states, leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analyses of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon.<br />In Brief Micali et al. report that human telencephalic NSCs in vitro transition through the organizer states that pattern the neocortex. Human pluripotent lines vary in organizer formation, generating divergent neuronal differentiation trajectories biased toward dorsal or ventral telencephalic fates and opening further analysis of the earliest cortical specification events.<br />Graphical Abstract
- Subjects :
- 0301 basic medicine
FGF2
EGFR
Neurogenesis
Induced Pluripotent Stem Cells
Biology
Inhibitory postsynaptic potential
Article
General Biochemistry, Genetics and Molecular Biology
neural stem cell
03 medical and health sciences
Glutamatergic
0302 clinical medicine
Neural Stem Cells
medicine
BMP
Humans
lcsh:QH301-705.5
Cells, Cultured
Embryonic Stem Cells
reproductive and urinary physiology
030304 developmental biology
Neurons
0303 health sciences
Cerebrum
Cell Differentiation
Neural stem cell
Cortex (botany)
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
nervous system
neural transcriptional dynamics
Cerebral cortex
Excitatory postsynaptic potential
Neuroscience
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cell reports, Cell Reports, Vol 31, Iss 5, Pp-(2020)
- Accession number :
- edsair.doi.dedup.....fb805a5b3d34d2c707163eee1a5b4e10