Article abstract


Nature Biotechnology 21, 1200 - 1207 (2003)
Published online: 21 September 2003 | doi:10.1038/nbt870

Neural subtype specification of fertilization and nuclear transfer embryonic stem cells and application in parkinsonian mice

Tiziano Barberi1,2, Peter Klivenyi3, Noel Y Calingasan3, Hyojin Lee1, Hibiki Kawamata3, Kathleen Loonam1, Anselme L Perrier1, Juan Bruses4, Maria E Rubio5, Norbert Topf6, Viviane Tabar1, Neil L Harrison6, M Flint Beal3, Malcolm A S Moore2 & Lorenz Studer1


Existing protocols for the neural differentiation of mouse embryonic stem (ES) cells require extended in vitro culture, yield variable differentiation results or are limited to the generation of selected neural subtypes. Here we provide a set of coculture conditions that allows rapid and efficient derivation of most central nervous system phenotypes. The fate of both fertilization- and nuclear transfer–derived ES (ntES) cells was directed selectively into neural stem cells, astrocytes, oligodendrocytes or neurons. Specific differentiation into gamma-aminobutyric acid (GABA), dopamine, serotonin or motor neurons was achieved by defining conditions to induce forebrain, midbrain, hindbrain and spinal cord identity. Neuronal function of ES cell–derived dopaminergic neurons was shown in vitro by electron microscopy, measurement of neurotransmitter release and intracellular recording. Furthermore, transplantation of ES and ntES cell–derived dopaminergic neurons corrected the phenotype of a mouse model of Parkinson disease, demonstrating an in vivo application of therapeutic cloning in neural disease.

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  1. Laboratory of Stem Cell and Tumor Biology, Division of Neurosurgery and Developmental Biology Program, Weill Medical College of Cornell University, New York, New York 10021, USA.
  2. James Ewing Laboratory for Developmental Hematopoiesis, Cell Biology Program, Sloan-Kettering Institute, Weill Medical College of Cornell University, New York, New York 10021, USA.
  3. Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
  4. Laboratory of Neural Development, Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA.
  5. Department of Physiology and Neurobiology, The University of Connecticut, Storrs, Connecticut 06269, USA.
  6. Departments of Anesthesiology and Pharmacology, Weill Medical College of Cornell University, New York, New York 10021, USA.

Correspondence to: Lorenz Studer1 e-mail: studerl@mskcc.org



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