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Neuron. 2014 Jul 2;83(1):69-86. doi: 10.1016/j.neuron.2014.05.035.

A quantitative framework to evaluate modeling of cortical development by neural stem cells.

Author information

1
Neurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
2
Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
3
Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
4
Center for Stem Cell Biology and Engineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
5
School of Medicine, Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA.
6
Molecular, Cellular and Developmental Biology and Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
7
Neurogenetics Program, Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dhg@mednet.ucla.edu.

Abstract

Neural stem cells have been adopted to model a wide range of neuropsychiatric conditions in vitro. However, how well such models correspond to in vivo brain has not been evaluated in an unbiased, comprehensive manner. We used transcriptomic analyses to compare in vitro systems to developing human fetal brain and observed strong conservation of in vivo gene expression and network architecture in differentiating primary human neural progenitor cells (phNPCs). Conserved modules are enriched in genes associated with ASD, supporting the utility of phNPCs for studying neuropsychiatric disease. We also developed and validated a machine learning approach called CoNTExT that identifies the developmental maturity and regional identity of in vitro models. We observed strong differences between in vitro models, including hiPSC-derived neural progenitors from multiple laboratories. This work provides a systems biology framework for evaluating in vitro systems and supports their value in studying the molecular mechanisms of human neurodevelopmental disease.

PMID:
24991955
PMCID:
PMC4277209
DOI:
10.1016/j.neuron.2014.05.035
[Indexed for MEDLINE]
Free PMC Article
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