[HTML][HTML] Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes

Hd iPsc Consortium - Cell stem cell, 2012 - cell.com
Hd iPsc Consortium
Cell stem cell, 2012cell.com
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 …
Summary
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.
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