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| Status |
Public on Jun 15, 2012 |
| Title |
GENETIC CORRECTION OF HUNTINGTON'S DISEASE PHENOTYPES IN INDUCED PLURIPOTENT STEM CELLS |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Huntington's Disease (HD) is caused by a CAG expansion in the huntingtin gene. Expansion of the polyglutamine tract in the huntingtin protein results in massive cell death in the striatum of HD patients. We report that human induced pluripotent stem cells (iPSCs) derived from HD patient fibroblasts can be corrected by replacing the expanded CAG repeat with a normal repeat using homologous recombination, and that the correction persists in iPSC differentiation into DARPP-32 positive neurons in vitro and vivo. Further, correction of the HD-iPSCs normalized pathogenic HD signaling pathways (cadherin, TGF-β, BNDF, caspase activation), and reversed disease phenotypes such as susceptibility to cell death and altered mitochondrial bioenergetics in neural stem cells. The ability to make patient-specific, genetically corrected iPSCs from HD patients will provide relevant disease models in identical genetic backgrounds and is a critical step for the eventual use of these cells in cell replacement therapy.
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| Overall design |
16 experimental samples were used overall. There were 8 replicates per group, with one group being the control, and the other being the experimental. Comparison was carried out on the Nimblegen platform.
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| Contributor(s) |
An MC, Zhang N, Scott G, Montoro D, Wittkop T, Mooney S, Melov S, Ellerby L |
| Citation(s) |
22748967 |
| Submission date |
Apr 24, 2012 |
| Last update date |
Jan 02, 2013 |
| Contact name |
Simon Melov |
| E-mail(s) |
smelov@buckinstitute.org
|
| Phone |
415 209 2068
|
| Organization name |
Buck Institute for Research on Aging
|
| Lab |
Melov Lab
|
| Street address |
8001 Redwood Blvd
|
| City |
Novato |
| State/province |
CA |
| ZIP/Postal code |
94945 |
| Country |
USA |
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| Platforms (1) |
| GPL15338 |
Nimblegen Homo sapiens HG18 Expression Array (12x135k) [gene-level] |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA161539 |
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