Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell 2012 Aug 03;11(2):264-78
Date
07/04/2012Pubmed ID
22748968Pubmed Central ID
PMC3804072DOI
10.1016/j.stem.2012.04.027Scopus ID
2-s2.0-84864628471 (requires institutional sign-in at Scopus site) 421 CitationsAbstract
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. Here, The HD Consortium reports the generation and characterization of 14 induced pluripotent stem cell (iPSC) lines from HD patients and controls. Microarray profiling revealed CAG-repeat-expansion-associated gene expression patterns that distinguish patient lines from controls, and early onset versus late onset HD. Differentiated HD neural cells showed disease-associated changes in electrophysiology, metabolism, cell adhesion, and ultimately cell death for lines with both medium and longer CAG repeat expansions. The longer repeat lines were however the most vulnerable to cellular stressors and BDNF withdrawal, as assessed using a range of assays across consortium laboratories. The HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a human stem cell platform for screening new candidate therapeutics.
Author List
HD iPSC ConsortiumAuthor
Allison D. Ebert PhD Center Director, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
HumansHuntington Disease
Induced Pluripotent Stem Cells
Phenotype
Trinucleotide Repeat Expansion
