Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/136086
Title: IN VITRO PARKINSON'S DISEASE MODELING USING HUMAN MIDBRAIN-LIKE ORGANOIDS
Authors: HOANG-DAI TRAN
Keywords: stem cells, genome editing, Parkinson's disease, neuronal differentiation, midbrain organoids, disease modeling
Issue Date: 19-Aug-2016
Source: HOANG-DAI TRAN (2016-08-19). IN VITRO PARKINSON'S DISEASE MODELING USING HUMAN MIDBRAIN-LIKE ORGANOIDS. ScholarBank@NUS Repository.
Abstract: Parkinson’s disease (PD) is one of the most common neurodegenerative movement disorders. Currently, the disease pathogenesis is not yet clear, although many studies have been conducted to investigate the mechanism of this disease. In this study, I optimized CRISPR/Cas9 system to generate mutations on several well-known PD-related genes, including PINK1 and PARK2, on human embryonic stem cell (ESC) and then characterized them. Next, I optimized the protocol to generate human midbrain-like organoids (hMLOs) from human pluripotent stem cells. The results demonstrated that hMLOs could reflect the development of human fetal midbrain, which gives rise to distinct layers of neuronal cells. More importantly, I was able to show that dopaminergic neurons within organoids are authentic and that prolonged culture of hMLOs can produce neuromelanin (NM). Finally, I also presented some preliminary data of PD modeling using this organoid system by using the generated knockout cell lines.
URI: http://scholarbank.nus.edu.sg/handle/10635/136086
Appears in Collections:Ph.D Theses (Restricted)

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