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

Publication ,  Journal Article
Lu, C; Shi, X; Allen, A; Baez-Nieto, D; Nikish, A; Sanjana, NE; Pan, JQ
Published in: FASEB J
April 2019

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.

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Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

April 2019

Volume

33

Issue

4

Start / End Page

5287 / 5299

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Patch-Clamp Techniques
  • Neurons
  • Nerve Tissue Proteins
  • Induced Pluripotent Stem Cells
  • Immunohistochemistry
  • Humans
  • Cell Line
  • Cell Differentiation
  • Biochemistry & Molecular Biology
 

Citation

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Lu, C., Shi, X., Allen, A., Baez-Nieto, D., Nikish, A., Sanjana, N. E., & Pan, J. Q. (2019). Overexpression of NEUROG2 and NEUROG1 in human embryonic stem cells produces a network of excitatory and inhibitory neurons. FASEB J, 33(4), 5287–5299. https://doi.org/10.1096/fj.201801110RR
Lu, Congyi, Xi Shi, Andrew Allen, David Baez-Nieto, Alexandria Nikish, Neville E. Sanjana, and Jen Q. Pan. “Overexpression of NEUROG2 and NEUROG1 in human embryonic stem cells produces a network of excitatory and inhibitory neurons.FASEB J 33, no. 4 (April 2019): 5287–99. https://doi.org/10.1096/fj.201801110RR.
Lu C, Shi X, Allen A, Baez-Nieto D, Nikish A, Sanjana NE, et al. Overexpression of NEUROG2 and NEUROG1 in human embryonic stem cells produces a network of excitatory and inhibitory neurons. FASEB J. 2019 Apr;33(4):5287–99.
Lu, Congyi, et al. “Overexpression of NEUROG2 and NEUROG1 in human embryonic stem cells produces a network of excitatory and inhibitory neurons.FASEB J, vol. 33, no. 4, Apr. 2019, pp. 5287–99. Pubmed, doi:10.1096/fj.201801110RR.
Lu C, Shi X, Allen A, Baez-Nieto D, Nikish A, Sanjana NE, Pan JQ. Overexpression of NEUROG2 and NEUROG1 in human embryonic stem cells produces a network of excitatory and inhibitory neurons. FASEB J. 2019 Apr;33(4):5287–5299.

Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

April 2019

Volume

33

Issue

4

Start / End Page

5287 / 5299

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Patch-Clamp Techniques
  • Neurons
  • Nerve Tissue Proteins
  • Induced Pluripotent Stem Cells
  • Immunohistochemistry
  • Humans
  • Cell Line
  • Cell Differentiation
  • Biochemistry & Molecular Biology