Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons

Embryonic stem (ES) cells represent a suitable model to analyze cell differentiation processes in vitro. Here, we report that pluripotent ES cells of the line BLC 6 differentiate in vitro into neuronal cells possessing the complex electrophysiological and immunocytochemical properties of postmitotic...

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Bibliographic Details
Published in:Mechanisms of development 1995-10, Vol.53 (2), p.275-287
Main Authors: Strübing, Carsten, Ahnert-Hilger, Gudrun, Shan, Jin, Wiedenmann, Bertram, Hescheler, Jürgen, Wobus, Anna M.
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Blastocyst - cytology
Cell Differentiation - physiology
Cell Line
Cell Lineage
Cellular Senescence - physiology
Inhibitory and excitatory synapses
Ion channels
Ion Channels - physiology
Mouse embryonic stem cells
Neuronal differentiation
Neurons - cytology
Patch-Clamp Techniques
Receptors, Cell Surface - physiology
Stem Cells - cytology
Synapses - physiology
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Summary:Embryonic stem (ES) cells represent a suitable model to analyze cell differentiation processes in vitro. Here, we report that pluripotent ES cells of the line BLC 6 differentiate in vitro into neuronal cells possessing the complex electrophysiological and immunocytochemical properties of postmitotic nerve cells. In the course of differentiation BLC 6-derived neurons differentially express voltagedependent (K +, Na +, Ca 2+) and receptor-operated (GABA A, glycine, AMPA, NMDA receptors) ionic channels. They generate fast Na +-driven action potentials and are functionally coupled by inhibitory (GABAergic) and excitatory (glutamatergic) synapses as revealed by measurements of postsynaptic currents. Moreover, BLC 6-derived neurons express neuron-specific cytoskeletal, cell adhesion and synaptic vesicle proteins and exhibit a Ca 2+-dependent GABA secretion. Thus, the ES cell model enables the investigation of cell lineage determination and signaling mechanisms in the developing nervous system from a pluripotential stem cell to a differentiated postmitotic neuron. The in vitro differentiation of neurons from ES cells may be an excellent approach to study by targeted gene disruption a variety of neuronal functions.
ISSN:0925-4773
1872-6356
DOI:10.1016/0925-4773(95)00446-8