Format

Send to

Choose Destination
Cell Stem Cell. 2012 Aug 3;11(2):253-63. doi: 10.1016/j.stem.2012.04.026. Epub 2012 Jun 28.

Genetic correction of Huntington's disease phenotypes in induced pluripotent stem cells.

Author information

1
The Buck Institute for Research on Aging, Novato, CA 94945, USA.

Abstract

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 the replacement of 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 in vivo. Further, correction of the HD-iPSCs normalized pathogenic HD signaling pathways (cadherin, TGF-β, BDNF, and 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.

PMID:
22748967
PMCID:
PMC3608272
DOI:
10.1016/j.stem.2012.04.026
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center