Derivation of homogeneous GABAergic neurons from mouse embryonic stem cells

Christina Chatzi, Roderick Hamilton Scott, Jin Pu, Bing Lang, Chizu Nakamoto, Colin Darnley McCaig, Sanbing Shen

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 similar to 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 markets 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. (C) 2009 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)407-416
Number of pages10
JournalExperimental Neurology
Volume217
Issue number2
Early online date5 Apr 2009
DOIs
Publication statusPublished - Jun 2009

Keywords

  • Embryonic stem cells
  • Embryoid body
  • GABAergic neurons
  • Retinoic acid
  • neural progenitor cells
  • midbrain dopaminergic-neurons
  • in-vitro differentiation
  • ES cells
  • directed differentiation
  • lineage selection
  • precursor cells
  • functional-properties
  • subventricular zone
  • motor-neurons
  • Embryonic stem cells

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