Transcriptional Regulation of Human Embryonic Stem Cells

Transcriptional Regulation of Human Embryonic Stem Cells

Funding Type: 
SEED Grant
Grant Number: 
RS1-00434
Award Value: 
$595,755
Stem Cell Use: 
Embryonic Stem Cell
Status: 
Closed
Public Abstract: 
Statement of Benefit to California: 
Progress Report: 

Year 1

A central goal of our CIRM SEED proposal was to use innovative unbiased approaches to discover novel proteins that turn genes on or off in pluripotent stem cells. An understanding of what are these proteins that act as genetic switches and how they function is of significant importance to efforts to use pluripotent stem cells to model disease states in the lab or to provide a source of cells of therapeutic interest for transplantation. We have been successful in our efforts, in that we identified a novel protein that appears to play an unexpected role in the regulation of gene activity in pluripotent stem cells. In addition, we have identified another protein that is critical to maintain the DNA of pluripotent stem cells is a state accessible to other proteins. Our research is therefore providing an integrated picture of what are the genetic switches that turn genes on or off in pluripotent stem cells, what genes do they regulate, and how is their access to DNA regulated. Some of our results have recently been published, while other research is ongoing. In parallel, we have been very successful at transferring expertise to the biotechnology sector in California. In particular, two highly qualified lab members accepted senior scientist positions at top biotechnology firms in California (iPierian and Genentech).

Year 2

A central goal of our CIRM SEED proposal was to use innovative approaches to discover genes that control human embryonic stem cells, with the idea that this knowledge may lead to improved methods for growth and/or differentiation of human pluripotent stem cells in a clinical setting. In the past year we have continued to make significant progress on these efforts. We have found a factor that acts to turn other genes on or off and is active in embryonic stem cells. We have put a considerable amount of effort into optimizing methods to identify exactly what genes this factor controls. Our results show that this factor directly regulates pluripotency-associated genes. This is remarkable, since this factor had not to date been implicated in the regulation of pluripotency. These results put us in a position to characterize the function of this factor in embryonic stem cells in greater detail. In addition, we are applying knowledge gained from our studies to develop methods to enhance the ease with which human pluripotent stem cells are propagated. Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, are notoriously more difficult to grow than their mouse counterparts, and this has significantly hampered the ability to use existing human pluripotent stem cells to model disease. We have developed conditions that facilitate the propagation of human pluripotent stem cells in a state that resembles mouse ES cells, where they are easier to propagate and grow more rapidly. These findings, while preliminary, suggest that we have the opportunity to explore a transition of human pluripotent stem cells to a state that is easier to culture and manipulate genetically. Thus, the CIRM SEED award has allowed us to discover a novel regulator of pluripotency genes, and to develop conditions that may lead to improved culture and manipulation of human pluripotent stem cells.

© 2013 California Institute for Regenerative Medicine