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


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.

DOI: 10.1016/j.stem.2012.04.027
Citations per Year

286 Citations

Semantic Scholar estimates that this publication has 286 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Mattis2012InducedPS, title={Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes.}, author={Virginia B. Mattis and Soshana P. Svendsen and Allison D. Ebert and Clive Niels Svendsen and Alvin R. King and Malcolm S. Casale and Sara Winokur and Gayani Batugedara and Marquis P. Vawter and Peter Donovan and Leslie F. Lock and Leslie M. Thompson and Ranjit Singh Atwal and Yu Zhu and Elisa Fossale and Tammy Gillis and Jayalakshmi Srinidhi Mysore and Jian-hong Li and IhnSik Seong and Yiping Shen and Xiaoli Chen and Vanessa C. Wheeler and Marcy E. MacDonald and James F. Gusella and Sergey S. Akimov and Nicolas Arbez and Tarja A Juopperi and Tamara Ratovitski and Jason H. Chiang and Woon Roung Kim and Ekaterine Chighladze and Erin E. Watkin and Chun Zhong and Georgia Makri and Robert N Cole and Russell L. Margolis and Hongjun Song and Guoli Ming and Christopher A. Ross and Julia A. Kaye and Aaron Daub and Punita Sharma and Amanda R. Mason and Steven M. Finkbeiner and David J. Rushton and Stephen P Brazier and Alysia A. Battersby and Amanda J Redfern and Hsui-Er Tseng and Alexander W. Harrison and Paul J Kemp and Nicholas D. Allen and Valentina Castiglioni and Marco Onorati and Elena Cattaneo and Junying Yu and James A. Thomson and Jamshid Arjomand and Alison Ebert}, journal={Cell stem cell}, year={2012}, volume={11 2}, pages={264-78} }