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

Fei Yi, Jing Qu, Mo Li, Keiichiro Suzuki, Na Young Kim, Guang Hui Liu, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)855-863
Number of pages9
JournalProtein and Cell
Volume3
Issue number11
DOIs
StatePublished - Nov 19 2012

Keywords

  • Wilson's disease
  • hepatocyte
  • induced pluripotent stem cell
  • neural stem cell
  • neuron

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Drug Discovery
  • Cell Biology

Fingerprint

Dive into the research topics of 'Establishment of hepatic and neural differentiation platforms of Wilson's disease specific induced pluripotent stem cells'. Together they form a unique fingerprint.

Cite this