The role of transcription factor GATA6 in the development of the human pancreas
type: CreativeWork
description: While there has been an opulence of data and studies surrounding the study of the developing pancreas in mammals and other vertebrates, the focus has largely been in mice. The paucity of research in the development of the human pancreas has led to diminished knowledge in the area, compared to other species. Recent discoveries provide growing evidence for discrepancies between mouse and human pancreatic development and diseases and highlight the fact that developmental studies of the pancreas in humans are imperative. The need to develop therapies for diabetes, a growing and one of the leading health problems worldwide, further compels more exploration in this area to deepen our understanding in the different aspects of diabetes in humans and its underlying causes. Research involving modelling human diseases in vitro enables the investigation of the cellular and molecular mechanisms underlying these diseases as well as the development of therapies for treating them. The availability of hPSCs brings with it the advantage of overcoming the limitations of animal models for certain disorders such as pancreatic agenesis, the focus of my project. The use of site-specific nucleases such as TALENs for such a purpose represents a paradigm shift in disease modelling, where TALENs are capable of directly correcting disease-causing mutations, therefore permanently eliminating the symptoms with precise genome modifications. Alternatively, TALENs can also be used to inactivate specific genes by inducing site-specific mutations. Using these tools, I found that GATA6 is required for the formation of the definitive endoderm (DE) and pancreas in humans; hPSCs harbouring homozygous GATA6 mutations fail to form the definitive endoderm, and consequently the pancreas, whereas hPSCs harbouring heterozygous GATA6 mutations exhibited impairment in definitive endoderm development, although it remains unclear if this is a protocol dependent defect. At the pancreatic stage, heterozygous GATA6 m…
abstract: While there has been an opulence of data and studies surrounding the study of the developing pancreas in mammals and other vertebrates, the focus has largely been in mice. The paucity of research in the development of the human pancreas has led to diminished knowledge in the area, compared to other species. Recent discoveries provide growing evidence for discrepancies between mouse and human pancreatic development and diseases and highlight the fact that developmental studies of the pancreas in humans are imperative. The need to develop therapies for diabetes, a growing and one of the leading health problems worldwide, further compels more exploration in this area to deepen our understanding in the different aspects of diabetes in humans and its underlying causes. Research involving modelling human diseases in vitro enables the investigation of the cellular and molecular mechanisms underlying these diseases as well as the development of therapies for treating them. The availability of hPSCs brings with it the advantage of overcoming the limitations of animal models for certain disorders such as pancreatic agenesis, the focus of my project. The use of site-specific nucleases such as TALENs for such a purpose represents a paradigm shift in disease modelling, where TALENs are capable of directly correcting disease-causing mutations, therefore permanently eliminating the symptoms with precise genome modifications. Alternatively, TALENs can also be used to inactivate specific genes by inducing site-specific mutations. Using these tools, I found that GATA6 is required for the formation of the definitive endoderm (DE) and pancreas in humans; hPSCs harbouring homozygous GATA6 mutations fail to form the definitive endoderm, and consequently the pancreas, whereas hPSCs harbouring heterozygous GATA6 mutations exhibited impairment in definitive endoderm development, although it remains unclear if this is a protocol dependent defect. At the pancreatic stage, heterozygous GATA6 m…
author: Chia, Crystal Ying
language: en
keywords: GATA6, pancreatic agenesis, haploinsufficiency, disease modelling
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/7928b3d2-f9ce-45e5-ae60-97097ad60c17/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2018-02-07
date modified: 2026-07-22T22:24:01Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.18840