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Title: | REGULATION OF CELL FATE VIA CHEMICAL MEANS | Authors: | JOHN TNG WEIQUAN | Keywords: | Organoids, stem cell, liver, reprogramming, disease modelling | Issue Date: | 19-Aug-2016 | Citation: | JOHN TNG WEIQUAN (2016-08-19). REGULATION OF CELL FATE VIA CHEMICAL MEANS. ScholarBank@NUS Repository. | Abstract: | Abstract Understanding disease mechanisms and development of new therapeutic strategies is reliant on disease models. Many existing in vitro models assume cell autonomous mechanisms of disease, but disease phenotypes or responses to drug may only evident if the complete sets of cell types in a tissue are present. Organoids are 3D structures containing lineage specific differentiated cells that better reflect the in vivo state and as such provide better disease models compared to their 2D counterparts. To date, human pluripotent stem cells (PSCs) have been coaxed to generate intestinal, kidney, brain and retinal organoids. However, liver organoids containing the two main hepatic cell types namely hepatocytes and cholangiocytes has yet to be derived from PSCs. In this thesis, we report the generation of multipotent endoderm spheroid progenitors (MESPs) as a scalable resource for the efficient derivation of liver organoids. Our preliminary data confirm that liver organoids derived with our protocol display cellular composition, structure and organization as well as metabolic function resembling that of the in vivo liver. Altogether, this study demonstrates that our organoid culture system have enormous potential not only to model liver development and metabolic liver diseases in vitro, but also to be used as an alternative system for drug testing that may better recapitulate effects in human patients and even cut down on animal studies. | URI: | http://scholarbank.nus.edu.sg/handle/10635/134629 |
Appears in Collections: | Ph.D Theses (Open) |
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Thesis v1.0 corrected following defense (1).pdf | 4.62 MB | Adobe PDF | OPEN | None | View/Download |
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