Disease-specific Induced Pluripotent Stem Cell Modeling: Insights into the Pathophysiology of Valosin Containing Protein (VCP) DiseaseEric Dec1,2,#, David Ferguson1,2,#, Angèle Nalbandian1,2,#, Matthew Gargus1, Veeral Katheria1, Prachi Rana1, Abel Ibrahim1, Maya Hatch2, Mary Lan1, Katrina J Llewellyn1, Hans Keirstead2 and Virginia E Kimonis1,2*
- Corresponding Author:
- Virginia Kimonis, MD, MRCP
Department of Pediatrics, Division of Genetics and Metabolism
University of California-Irvine, 2501 Hewitt Hall, Irvine, CA 92697, USA
Tel: (714) 456-5791, (714) 456-2942
Fax: (714) 456-5330;
Pager: (714) 506-2063
E-mail: [email protected]
Received Date: January 05, 2014; Accepted Date: February 09, 2014; Published Date: February 11, 2014
Citation: Dec E, Ferguson D, Nalbandian A, Gargus M, Katheria V, et al. (2014) Disease-Specific Induced Pluripotent Stem Cell Modeling: Insights into the Pathophysiology of Valosin Containing Protein (VCP) Disease. J Stem Cell Res Ther 4:168. doi: 10.4172/2157-7633.1000168
Copyright: © 2014 Dec E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Valosin Containing Protein (VCP) disease is an autosomal dominant disorder caused by mutations in the VCP gene and is associated with progressive muscle weakness and atrophy. Affected individuals exhibit striking scapular winging due to shoulder girdle weakness. Currently, there are no treatments available and patients are dying early from cardiac and respiratory failure, typically in their 40’s and 50’s. The generation of disease-specific induced pluripotent stem cells (iPSC) offers a novel platform to investigate mechanisms of VCP disease and potential treatments similar to other disease models including Amyotrophic Lateral Sclerosis (ALS), Duchenne muscular dystrophy (DMD), Parkinson’s disease, Alzheimer’s disease (AD), Best Disease (BD), and type I juvenile diabetes mellitus (T1DM). Herein, we report the generation and characterization of a human iPSC line to examine the cellular and molecular processes underlying VCP disease. The VCP iPSC line expressed specific pluripotency markers NANOG, SSEA4, OCT-4, TRA-1-81 and exhibited characteristic morphology. We differentiated the human iPSC cell line into a neuronal lineage confirmed by TUJ-1 staining, a neuronal class III β-tubulin marker. We detected higher protein expression levels of ubiquitin (Ub), TAR DNA binding protein-43 (TDP-43), Light Chain 3-I/II (LC3), p62/SQSTM1, and optineurin (OPN) in the iPSC neural lineage compared to the control neural line. Collectively, our results demonstrate that patient-specific iPSC technology may provide useful disease modeling for understanding the complex mechanisms and for novel treatments of VCP and related disorders.