Department of Anesthesiology

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Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells.

TitleDirected differentiation and functional maturation of cortical interneurons from human embryonic stem cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsMaroof AM, Keros S, Tyson JA, Ying S-W, Ganat YM, Merkle FT, Liu B, Goulburn A, Stanley EG, Elefanty AG, Widmer HRuedi, Eggan K, Goldstein PA, Anderson SA, Studer L
JournalCell Stem Cell
Volume12
Issue5
Pagination559-72
Date Published2013 May 2
ISSN1875-9777
Abstract

Human pluripotent stem cells are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations: projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism, and epilepsy. Here, we demonstrate the highly efficient derivation of human cortical interneurons in an NKX2.1::GFP human embryonic stem cell reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neurotransmitter phenotypes, and migratory behaviors. Further differentiation in a murine cortical environment yields parvalbumin- and somatostatin-expressing neurons that exhibit synaptic inputs and electrophysiological properties of cortical interneurons. Our study defines the signals sufficient for modeling human ventral forebrain development in vitro and lays the foundation for studying cortical interneuron involvement in human disease pathology.

DOI10.1016/j.stem.2013.04.008
Alternate JournalCell Stem Cell
PubMed ID23642365
PubMed Central IDPMC3681523
Grant ListR01 MH066912 / MH / NIMH NIH HHS / United States
R01 NS066390 / NS / NINDS NIH HHS / United States
RC1 MH089690 / MH / NIMH NIH HHS / United States