Induced Accelerated Aging in Induced Pluripotent Stem Cell Lines from Patients with Parkinson's Disease

The overall goal of the study was to develop a cell culture system from patient-derived induced pluripotent stem cells that expresses genes that can accelerate the aging process to facilitate modeling of neurodegenerative diseases such as Parkinson s disease. The objective of this study was to introduce the truncated lamin A gene, progerin, into patient-derived induced pluripotent stem cells using a doxycycline (Dox)-inducible expression system and differentiate them into dopaminergic neurons with the goal to accelerate the aging process of these cells and to promote a PD-related phenotype thus establishing a disease-in-a-dish model for PD. During our study, a publication from Lorenz Studer showed a very similar approach with lentiviral constructs of truncated lamin A in iPSC-differentiated neurons (Miller et al. 2013). It shows that our hypothesis is correct and that the introduction of mutant forms of lamin A that can cause Hutchinson Gilford Progeria syndrome is accelerating the neurodegenerative phenotype in vitro.
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