Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids

Non-alcoholic fatty liver disease (NAFLD) is described as a global epidemic. With no approved drugs in the market, the disease imposes huge economic and healthcare burden to the society. In-vitro models are deemed as a potential method to test and screen drugs. Hepatic organoids (HOs) differentiated...

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Main Author: Lim, Yee Siang
Other Authors: -
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2020
Subjects:
Online Access:https://hdl.handle.net/10356/139651
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author Lim, Yee Siang
author2 -
author_facet -
Lim, Yee Siang
author_sort Lim, Yee Siang
collection NTU
description Non-alcoholic fatty liver disease (NAFLD) is described as a global epidemic. With no approved drugs in the market, the disease imposes huge economic and healthcare burden to the society. In-vitro models are deemed as a potential method to test and screen drugs. Hepatic organoids (HOs) differentiated from adult stem cells derived from the liver are attractive in-vitro models due to its ability to recapitulate functions of the liver. In-vitro models were established using tissues from Non-alcoholic steatohepatitis (NASH) patients and healthy donors. A transcriptomics approach was taken to determine if HOs from NASH donors can better recapitulate the disease in-vitro. It was discovered that NASH HOs have increased expression of genes associated to NASH. Inducing steatosis resulted in distinct upregulation of genes in NASH HOs which are associated to worse outcome in NAFLD patients. Together, the analysis suggests that HOs from NASH donors are better in-vitro models to recapitulate NAFLD.
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spelling ntu-10356/1396512023-02-28T18:33:47Z Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids Lim, Yee Siang - School of Biological Sciences Genome Institute of Singapore Ng Huck Hui nghh@ntu.edu.sg Science::Biological sciences Non-alcoholic fatty liver disease (NAFLD) is described as a global epidemic. With no approved drugs in the market, the disease imposes huge economic and healthcare burden to the society. In-vitro models are deemed as a potential method to test and screen drugs. Hepatic organoids (HOs) differentiated from adult stem cells derived from the liver are attractive in-vitro models due to its ability to recapitulate functions of the liver. In-vitro models were established using tissues from Non-alcoholic steatohepatitis (NASH) patients and healthy donors. A transcriptomics approach was taken to determine if HOs from NASH donors can better recapitulate the disease in-vitro. It was discovered that NASH HOs have increased expression of genes associated to NASH. Inducing steatosis resulted in distinct upregulation of genes in NASH HOs which are associated to worse outcome in NAFLD patients. Together, the analysis suggests that HOs from NASH donors are better in-vitro models to recapitulate NAFLD. Doctor of Philosophy 2020-05-20T12:37:29Z 2020-05-20T12:37:29Z 2019 Thesis-Doctor of Philosophy Lim, Y. S. (2019). Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/139651 10.32657/10356/139651 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
spellingShingle Science::Biological sciences
Lim, Yee Siang
Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids
title Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids
title_full Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids
title_fullStr Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids
title_full_unstemmed Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids
title_short Modelling non-alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids
title_sort modelling non alcoholic fatty liver disease using patient derived liver stem cells and hepatic organoids
topic Science::Biological sciences
url https://hdl.handle.net/10356/139651
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