Derivation of homogeneous GABAergic neurons from mouse embryonic stem cells

Christina Chatzi; Roderick H. Scott; Jin Pu; Bing Lang; Chizu Nakamoto; Colin D. McCaig; Sanbing Shen

doi:10.1016/j.expneurol.2009.03.032

Derivation of homogeneous GABAergic neurons from mouse embryonic stem cells

Christina Chatzi, Roderick H. Scott, Jin Pu, Bing Lang, Chizu Nakamoto, Colin D. McCaig, Sanbing Shen

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

Embryonic stem cells (ESCs) promise an unlimited source of defined cells for cell transplantation therapy, while protocols for derivation of homogeneous populations of desirable cell types are yet to be developed and/or refined. Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system, and disturbed GABAergic signaling is associated with a host of neurological conditions. We developed a simple ES cell differentiation protocol which led to the production of uniform GABAergic neurons in ∼ 2 weeks. The differentiation protocol involved treatment of embryoid bodies (EBs) with high concentrations (10^-5-10^-4 M) of all-trans-retinoic acid (RA) for 3 days. After plating these EBs on attached dishes in neural supportive medium, 93-96% of the cells became GABA-positive neurons in 7-11 days. These cells also expressed immature neuronal markers with voltage-gated delayed rectifier potassium currents, suggesting that they were immature GABAergic neurons. The technology may have implications for modeling and treatment of GABAergic signaling-related diseases and injuries.

Original language	English (US)
Pages (from-to)	407-416
Number of pages	10
Journal	Experimental Neurology
Volume	217
Issue number	2
DOIs	https://doi.org/10.1016/j.expneurol.2009.03.032
State	Published - Jun 2009
Externally published	Yes

Keywords

Embryoid body
Embryonic stem cells
GABAergic neurons
Retinoic acid

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

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10.1016/j.expneurol.2009.03.032

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title = "Derivation of homogeneous GABAergic neurons from mouse embryonic stem cells",

abstract = "Embryonic stem cells (ESCs) promise an unlimited source of defined cells for cell transplantation therapy, while protocols for derivation of homogeneous populations of desirable cell types are yet to be developed and/or refined. Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system, and disturbed GABAergic signaling is associated with a host of neurological conditions. We developed a simple ES cell differentiation protocol which led to the production of uniform GABAergic neurons in ∼ 2 weeks. The differentiation protocol involved treatment of embryoid bodies (EBs) with high concentrations (10-5-10-4 M) of all-trans-retinoic acid (RA) for 3 days. After plating these EBs on attached dishes in neural supportive medium, 93-96% of the cells became GABA-positive neurons in 7-11 days. These cells also expressed immature neuronal markers with voltage-gated delayed rectifier potassium currents, suggesting that they were immature GABAergic neurons. The technology may have implications for modeling and treatment of GABAergic signaling-related diseases and injuries.",

keywords = "Embryoid body, Embryonic stem cells, GABAergic neurons, Retinoic acid",

author = "Christina Chatzi and Scott, {Roderick H.} and Jin Pu and Bing Lang and Chizu Nakamoto and McCaig, {Colin D.} and Sanbing Shen",

note = "Funding Information: We thank the UK Medical Research Council, NHS Grampian and University of Aberdeen for funding the project. ",

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AU - Scott, Roderick H.

AU - Pu, Jin

AU - Lang, Bing

AU - Nakamoto, Chizu

AU - McCaig, Colin D.

AU - Shen, Sanbing

N1 - Funding Information: We thank the UK Medical Research Council, NHS Grampian and University of Aberdeen for funding the project.

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N2 - Embryonic stem cells (ESCs) promise an unlimited source of defined cells for cell transplantation therapy, while protocols for derivation of homogeneous populations of desirable cell types are yet to be developed and/or refined. Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system, and disturbed GABAergic signaling is associated with a host of neurological conditions. We developed a simple ES cell differentiation protocol which led to the production of uniform GABAergic neurons in ∼ 2 weeks. The differentiation protocol involved treatment of embryoid bodies (EBs) with high concentrations (10-5-10-4 M) of all-trans-retinoic acid (RA) for 3 days. After plating these EBs on attached dishes in neural supportive medium, 93-96% of the cells became GABA-positive neurons in 7-11 days. These cells also expressed immature neuronal markers with voltage-gated delayed rectifier potassium currents, suggesting that they were immature GABAergic neurons. The technology may have implications for modeling and treatment of GABAergic signaling-related diseases and injuries.

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Derivation of homogeneous GABAergic neurons from mouse embryonic stem cells

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Keywords

ASJC Scopus subject areas

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