Generating Late-Onset Human iPSC-Based Disease Models by Inducing Neuronal Age-Related Phenotypes through Telomerase Manipulation

Elsa Vera; Nazario Bosco; Lorenz Studer

Generating Late-Onset Human iPSC-Based Disease Models by Inducing Neuronal Age-Related Phenotypes through Telomerase Manipulation

2016

Elsa Vera | Nazario Bosco | Lorenz Studer

Modeling late-onset disorders such as Parkinson’s disease (PD) using iPSC technology remains a challenge, as current differentiation protocols yield cells with the properties of fetal-stage cells. Here, we tested whether it is possible to accelerate aging in vitro to trigger late-onset disease phenotypes in an iPSC model of PD. In order to manipulate a factor that is involved in natural aging as well as in premature aging syndromes, we used telomere shortening as an age-inducing tool. We show that shortened telomeres result in age-associated as well as potentially disease-associated phenotypes in human pluripotent stem cell (hPSC)-derived midbrain dopamine (mDA) neurons. Our approach provides proof of concept for the further validation of telomere shortening as an induced-aging tool for late-onset-disease modeling.

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