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Stem Cell Reports. 2014 Feb 27;2(3):295-310. doi: 10.1016/j.stemcr.2014.01.009. eCollection 2014 Mar 11.

Modeling hippocampal neurogenesis using human pluripotent stem cells.

Author information

The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neuroscience Discovery, Novartis Pharma AG, Novartis Institute for Biomedical Research, Postfach, Basel CH-4002, Switzerland.
Department of Neuroscience/Psychiatry, Mount Sinai School of Medicine, 1425 Madison Ave, New York, NY 10059, USA.

Erratum in

  • Stem Cell Reports. 2014 Jul 8;3(1):217.


The availability of human pluripotent stem cells (hPSCs) offers the opportunity to generate lineage-specific cells to investigate mechanisms of human diseases specific to brain regions. Here, we report a differentiation paradigm for hPSCs that enriches for hippocampal dentate gyrus (DG) granule neurons. This differentiation paradigm recapitulates the expression patterns of key developmental genes during hippocampal neurogenesis, exhibits characteristics of neuronal network maturation, and produces PROX1+ neurons that functionally integrate into the DG. Because hippocampal neurogenesis has been implicated in schizophrenia (SCZD), we applied our protocol to SCZD patient-derived human induced pluripotent stem cells (hiPSCs). We found deficits in the generation of DG granule neurons from SCZD hiPSC-derived hippocampal NPCs with lowered levels of NEUROD1, PROX1, and TBR1, reduced neuronal activity, and reduced levels of spontaneous neurotransmitter release. Our approach offers important insights into the neurodevelopmental aspects of SCZD and may be a promising tool for drug screening and personalized medicine.

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