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 journalArticlepeer-review

34 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 languageEnglish (US)
Pages (from-to)407-416
Number of pages10
JournalExperimental Neurology
Volume217
Issue number2
DOIs
StatePublished - Jun 2009
Externally publishedYes

Keywords

  • Embryoid body
  • Embryonic stem cells
  • GABAergic neurons
  • Retinoic acid

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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