The functional role of protein O-GlcNAcylation in hESC pluripotency and differentiation
Human embryonic stem cells can be changed into virtually any cell type in the adult body. Because of this unique capability, stem cells have the potential to cure a vast majority of existing human disorders. However, the mechanisms that govern the definition and function of stem cells has not been completely elucidated, and several hurdles exist and need to be overcome before stem cells can be used in the clinic. For example, the factors which govern the conversion of stem cells into a variety of tissue types such as liver, heart, and brain tissue - are not well understood. Our research employs a unique multidisciplinary approach to bridge this information gap. Proteins govern the daily life of cells by controlling when genes are activated, how cells communicate with one another, and several other critical processes. The action of proteins inside cells is commonly turned on and off by the appending to, or removal of, sugars from proteins. Though this control mechanism is well established in other areas of health and human disease, it has not been widely studied in the context of stem cell biology. The proposed research will examine how the sugars found on proteins impact processes such as the differentiation of stem cells into neurons, the generation of pluripotent stem cells, and how the genetic reprogramming of stem cells is actually carried out by cellular proteins. The results of these studies may lead to a greatly increased understanding of how stem cells retain their ability to be changed into other cell types, and also how the fate of stem cells is decided upon differentiation. Both are critical areas that need to be explored to enable modern regenerative medicine to realize its full potential as a tool for the treatment of human diseases.
Programs funded by CIRM and other state granting agencies will allow California to continue to be at the frontier of stem cell research for the development of new treatments to cure human diseases. Research such as ours will hopefully enable modern medicine to access exciting new areas such as spinal regeneration, and finding treatments for neurodegenerative disorders for which there is currently little hope for curing. Some illnesses which could be potentially impacted include multiple sclerosis, Alzheimer’s, Parkinson, and Batten diseases. Several hurdles exist, however, which need to be overcome before results from the exciting field of stem cell research can be used in the clinic. For example, the factors which govern conversion of stem cells into a variety of tissue types that may find uses in regenerative medicine such as the liver, heart, and brain, are not well understood. Our research employs a unique multidisciplinary approach to bridge this information gap. In particular, our research will examine how the sugars which are attached to proteins control processes such as the vast genetic reprogramming that accompanies the conversion of stem cells into mature tissues. Through initiatives like CIRM, California will continue to lead the nation in the discoveries resulting from multidisciplinary scientific research which will fuel tomorrow’s medical advances.