Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells

By Diana Yu, F. D. Di Giorgio, Jun Yao, M. Marchetto, K. Brennand, Rebecca Wright, Arianna Mei, Lauren Mchenry, David Lisuk, J. M. Grasmick and 4 more. 2014

257 citations recorded by the source corpus.

Summary 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.

Subfields: Developmental Neuroscience, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Developmental Neuroscience

1. R. Hen
2. Fred H. Gage
3. A. Dwork
4. G. Rosoklija
5. V. Arango
6. M. Boldrini
7. Sarah L. Parylak
8. Sara B. Linker

In Molecular Biology

1. R. Hen
2. Fred H. Gage
3. Hongjun Song

Citations in the corpus

• Human Hippocampal Neurogenesis Persists throughout Aging (2018, positive): “Unchanged nestin+ and Sox2/nestin+ cells, representing type I-II INPs (Yu et al., 2014), in older age, with preserved Ki-67+ cell numbers, suggest maintained proliferative capacity in healthy aging, perhaps compensating for a smaller QNP pool as an adaptive response to ageassociated social isolation”
• The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “Iwano T, Masuda A, Kiyonari H, Enomoto H, Matsuzaki F. Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus.”
• Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. (2016, unknown): “This in vitro system has recently been used tomodel Cell 167, November 3, 2016 909 mental disorders such as schizophrenia and bipolar disorder (Mertens et al., 2015; Yu et al., 2014).”