Open AccessHydroxyurea Facilitates Manifestation of Disease Relevant Phenotypes in Patients-Derived IPSCs-Based Modeling of Late-Onset Parkinson’s Disease
Author(s) -
Yuan Tan,
Minjing Ke,
Zhijian Huang,
Cheong-Meng Chong,
Xiaotong Cen,
Jiahong Lu,
Xiao-li Yao,
Dajiang Qin,
Huanxing Su
Publication year - 2019
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2018.1216
Subject(s) - induced pluripotent stem cell , dopaminergic , reprogramming , phenotype , disease , neurite , medicine , neuroscience , parkinson's disease , phenotypic screening , dopamine , biology , pharmacology , cancer research , cell , genetics , embryonic stem cell , in vitro , gene
Induced pluripotent stem cells (iPSCs)-derived dopaminergic neurons might be reset back to the fetal state due to reprogramming. Thus, it is a compelling challenge to reliably and efficiently induce disease phenotypes of iPSCs-derived dopaminergic neurons to model late-onset Parkinson's disease (PD). Here, we applied a small molecule, hydroxyurea (HU), to promote the manifestation of disease relevant phenotypes in iPSCs-based modeling of PD. We established two iPS cell lines derived from two sporadic PD patients. Both patients-iPSCs-derived dopaminergic neurons did not display PD relevant phenotypes after 6 weeks culture. HU treatment remarkably induced ER stress on patients-iPSCs-derived dopaminergic neurons. Moreover, HU treatment significantly reduced neurite outgrowth, decreased the expression of p-AKT and its downstream targets (p-4EBP1 and p-ULK1), and increased the expression level of cleaved-Caspase 3 in patients-iPSCs-derived dopaminergic neurons. The findings of the present study suggest that HU administration could be a convenient and reliable approach to induce disease relevant phenotypes in PD-iPSCs-based models, facilitating to study disease mechanisms and test drug effects.