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FASEB J. 2019 Jan 30:fj201801110RR. doi: 10.1096/fj.201801110RR. [Epub ahead of print]

Overexpression of NEUROG2 and NEUROG1 in human embryonic stem cells produces a network of excitatory and inhibitory neurons.

Author information

1
Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts, USA.
2
New York Genome Center, New York, New York, USA.
3
McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.
4
Department of Biology, New York University, New York, New York, USA.
5
Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.

Abstract

Overexpression of mouse neurogenin ( Neurog) 2 alone or in combination with mouse Neurog2/1 in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can rapidly produce high-yield excitatory neurons. Here, we report a detailed characterization of human neuronal networks induced by the expression of human NEUROG2 together with human NEUROG2/1 in hESCs using molecular, cellular, and electrophysiological measurements over 60 d after induction. Both excitatory synaptic transmission and network firing activity increased over time. Strikingly, inhibitory synaptic transmission and GABAergic cells were identified from NEUROG2/1 induced neurons (iNs). To illustrate the application of such iNs, we demonstrated that the heterozygous knock out of SCN2A, whose loss-of-function mutation is strongly implicated in autism risk, led to a dramatic reduction in network activity in the NEUROG2/1 iNs. Our findings not only extend our understanding of the NEUROG2/1-induced human neuronal network but also substantiate NEUROG2/1 iNs as an in vitro system for modeling neuronal and functional deficits on a human genetic background.-Lu, C., Shi, X., Allen, A., Baez-Nieto, D., Nikish, A., Sanjana, N. E., Pan, J. Q. Overexpression of NEUROG2 and NEUROG1 in human embryonic stem cells produces a network of excitatory and inhibitory neurons.

KEYWORDS:

; GABAergic; induced neuronal network; neurogenin

PMID:
30698461
DOI:
10.1096/fj.201801110RR

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