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. 2012 Jul 18;3(11):855–863. doi: 10.1007/s13238-012-2064-z

Establishment of hepatic and neural differentiation platforms of Wilson’s disease specific induced pluripotent stem cells

Fei Yi 1, Jing Qu 1, Mo Li 1, Keiichiro Suzuki 1, Na Young Kim 1, Guang-Hui Liu 1,2, Juan Carlos Izpisua Belmonte 1,3,✉
PMCID: PMC4875456  PMID: 22806248

Abstract

The combination of disease-specific human induced pluripotent stem cells (iPSC) and directed cell differentiation offers an ideal platform for modeling and studying many inherited human diseases. Wilson’s disease (WD) is a monogenic disorder of toxic copper accumulation caused by pathologic mutations of the ATP7B gene. WD affects multiple organs with primary manifestations in the liver and central nervous system (CNS). In order to better investigate the cellular pathogenesis of WD and to develop novel therapies against various WD syndromes, we sought to establish a comprehensive platform to differentiate WD patient iPSC into both hepatic and neural lineages. Here we report the generation of patient iPSC bearing a Caucasian population hotspot mutation of ATP7B. Combining with directed cell differentiation strategies, we successfully differentiated WD iPSC into hepatocyte-like cells, neural stem cells and neurons. Gene expression analysis and cDNA sequencing confirmed the expression of the mutant ATP7B gene in all differentiated cells. Hence we established a platform for studying both hepatic and neural abnormalities of WD, which may provide a new tool for tissue-specific disease modeling and drug screening in the future.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-012-2064-z and is accessible for authorized users.

Keywords: induced pluripotent stem cell, Wilson’s disease, hepatocyte, neural stem cell, neuron

Electronic supplementary material

13238_2012_2064_MOESM1_ESM.pdf (67.4KB, pdf)

Supplementary material, approximately 67.4 KB.

Footnotes

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-012-2064-z and is accessible for authorized users.

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Supplementary Materials

13238_2012_2064_MOESM1_ESM.pdf (67.4KB, pdf)

Supplementary material, approximately 67.4 KB.

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