University of Georgia

hESC Platform

Investigators

Stephen Dalton, Senior Investigator

Richard Steet, Senior Investigator

Overview

 

This program provides various cells for use in developing the technologies, methodologies, and software that drive the various Technology Research and Development projects in our Resource. Each batch of each cell type is analyzed by several types of assays before it is use for other studies in order to assure standardization and quality control. Sufficient quantities of each cell type are subjected to study by our other programs in order that adequate statistical confidence in the results are achieved. Human embryonic stem cells that have been differentiated to various differentiated states have been provided by the program. Some of these, along with various markers used to define a particular cell type, are shown in the figure below. In addition, fibroblasts from patients with various Congenital Disorders of Glycosylation have been reprogrammed to iPSC (induced pluripotent stem cells) and differentiated to some of the cell types depicted in order to allow investigators to study the effects of mutations on particular cellular phenotypes.

Human Embryonic Stem Cell Differentiation

Early cell fate diagram

Stephen Dalton, Director of UGA’s new Center for Molecular Medicine and Senior Investigator in the NCBG, is a leader in the study of human embryonic stem cell differentiation down the mesoderm and endoderm pathways. Many of the differentiated lines are available for distribution.

Richard Steet has worked with many researchers to investigate several primary cell lines derived from patients with Congenital Disorders of Glycosylation. In collaboration with Dr. Dalton, reprogrammed induced pluripotent cells have been produced from CDG fibroblasts in order to study how their genotypic defects give rise to phenotypic effects.

Major advances achieved by TR&D1 include the generation of iPSC and iPSC-derived cell models for four different glycosylation-related disorders. Our investigation of these lines is beginning to provide the first insight into the basis for cell type specific defects in glycosylation that is found in these disorders. These tools are also being used to investigate sensitive pathways in specialized cell types in a manner that were not possible with patient fibroblasts. Through dissemination of these findings, we are now recognized as a critical resource for the development of these cell models in a scale and quality that is necessary to address the key research questions. These models hold the potential to identify new targets for therapy to treat these disorders. As an example, we identified hepatocyte-specific deficits in glycosylation in CDG disorders. The development of hepatocyte models for PMM2-CDG and other CDGs has revealed – for the first time – emergent glycosylation defects within this cell lineage. The ability to develop a faithful cell model for CDGs is critical in the testing a novel therapeutic strategies that are currently under development by several groups.”