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Hydroxyurea Facilitates Manifestation of Disease Relevant Phenotypes in Patients-Derived IPSCs-Based Modeling of Late-Onset Parkinson’s Disease
Yuan Tan1; Minjing Ke1; Zhijian Huang1; Cheong-Meng Chong1; Xiaotong Cen2; Jia-Hong Lu1; Xiaoli Yao3; Dajiang Qin2; Huanxing Su1
2019-10
Source PublicationAGING AND DISEASE
ISSN2152-5250
Volume10Issue:5Pages:1037-1048
Abstract

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.

KeywordDisease Phenotypes Er Stress Induced Pluripotentstem Cells Parkinson’s Disease Hydroxyurea
DOI10.14336/AD.2018.1216
Indexed BySCI
Language英语
WOS Research AreaGeriatrics & Gerontology
WOS SubjectGeriatrics & Gerontology
WOS IDWOS:000488236800010
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorHuanxing Su
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
3.Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yuan Tan,Minjing Ke,Zhijian Huang,et al. Hydroxyurea Facilitates Manifestation of Disease Relevant Phenotypes in Patients-Derived IPSCs-Based Modeling of Late-Onset Parkinson’s Disease[J]. AGING AND DISEASE,2019,10(5):1037-1048.
APA Yuan Tan.,Minjing Ke.,Zhijian Huang.,Cheong-Meng Chong.,Xiaotong Cen.,...&Huanxing Su.(2019).Hydroxyurea Facilitates Manifestation of Disease Relevant Phenotypes in Patients-Derived IPSCs-Based Modeling of Late-Onset Parkinson’s Disease.AGING AND DISEASE,10(5),1037-1048.
MLA Yuan Tan,et al."Hydroxyurea Facilitates Manifestation of Disease Relevant Phenotypes in Patients-Derived IPSCs-Based Modeling of Late-Onset Parkinson’s Disease".AGING AND DISEASE 10.5(2019):1037-1048.
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