Control of human Embryonic Stem Cell Pluripotence and Fate Choice

Funding Type: 
Comprehensive Grant
Grant Number: 
RC1-00128
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
Control of human embryonic stem cell pluripotence and fate choice. A major goal for California's supporters of stem cell research is development of stem cell-based products that have medical use, and the mandate for the research community is to provide the best possible fundamental information to help guide clinical applications. Our research plan is to lay the groundwork for medical use of stem cells by an ambitious program to address the most important basic questions about stem cells. How do different stem cell lines differ from each other, and which one is best for a particular therapy or product? What gives stem cells the ability to self-renew? Can we make stem cells into the adult cell types we need? Can stem cells be made safe- what causes some stem cells to form tumors? We will use "high-throughput" techniques developed for the Human Genome Project to examine a large group of human embryonic stem (ES) cells and related cells. The techniques show us how all 25,000 genes in the human genome are turned on and off in different cell types. We were surprised to learn that embryonic stem cells from all over the world all have almost the same gene activity pattern- they have more genes "on" than any other cell type. As the ES cells develop into particular types of cells, like nerve cells or muscle cells, they turn off particular genes and turn on others. We used bioinformatics, which merges computer science and biology, to examine huge amounts of data, (millions of data points), and discovered the processes of self-renewal and differentiation seem to be tightly regulated by many types of molecular signals. The goal of our research proposal is to understand how these signals work, and to intervene in the signaling to discover how to control the development of stem cells so that they can be both safe and effective for medical applications. We believe that scientific data aren't useful unless they can be used by other scientists to guide their experiments, so we will publish our molecular information on a web-based knowledge database, which can be shared by stem cell scientists all over the world. If we achieve our aims, scientists and clinicians will be able to find out with a click of a mouse which stem cells they should use for studying Alzheimer's disease, which cells to use for testing the effects of new drugs, and which cells will be safe and efficacious when transplanted to the brain of a child with a fatal neurological disease.
Statement of Benefit to California: 
Californians are a large and diverse population that poses unique challenges for the future of medical care. Fortunately, California has a tradition of taking the lead in technology and medical breakthroughs and following through from the first idea to the final product. A major goal for California's supporters of stem cell research is development of stem cell-based products that have medical use, and the mandate for the research community is to provide the best possible fundamental information to help guide clinical applications. Our research plan is to lay the groundwork for medical use of stem cells by an ambitious program to address the most important basic questions about stem cells. How do different stem cell lines differ from each other, and which one is best for a particular therapy or product? What gives stem cells the ability to self-renew? Can we make stem cells into the adult cell types we need? Can stem cells be made safe- what causes some stem cells to form tumors? We will use "high-throughput" techniques developed for the Human Genome Project to examine a large group of human embryonic stem cells and related cells. The huge amount of information we generate will be used to create a web-based shared knowledge database. The publicly accessible knowledge database will provide answers for many of the existing questions and inspire new ones. This innovative program has the potential to make California a significant stem cell and life science content provider. It will be a magnet for other researchers, inside and outside California, to contribute their own information and expertise, which will leverage the power of the California stem cell community to explore novel approaches. The proposed project will also be a springboard to new commercial ventures, and attract investment in research and development. Ultimately the project will speed the development of clinical applications for stem cells that will benefit all Californians.

© 2013 California Institute for Regenerative Medicine