Whole-genome analysis of sequence variation in stem cell culture and differentiation

Funding Type: 
Basic Biology IV
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Stem cell biology is expected to bring great progress both in basic biomedical research and also eventually by providing personalized treatments and cures for many diseases, including some of the most severe ones. However, there is evidence accumulating that perhaps the genome structure of stem cells in culture is not always completely stable. If this is a widespread phenomenon then it could confuse the results coming out of basic research that is making use of stem cells. And also it could have severe consequences for the patient, if a stem cell line is used in a treatment that has some instability in its genome which could render the treatment useless - or even dangerous to the patient, since genome instability can under certain conditions make cell lines become cancerous.
There are new and powerful DNA analysis instruments available that allow for the first time to capture all genome variation and potential instability in a cell and we propose to make use of those instruments to study the genomes in a variety of different stem cell lines while they are kept in culture over extended periods as time and also while they are turned into neuronal and heart muscle tissue. We will be able to detect and measure genomic instability or variability if it exists and we will also be able to determine what, if any, the effects of such variability could be on the molecular mechanisms of control inside the cells.

Statement of Benefit to California: 

Both stem cell biology and genomics technology are developing at a very fast pace and the breakthroughs in each field can be called revolutionary. Furthermore it is to be expected that it will be at the confluence of the two fields where some of the largest benefits for both basic research and translational medicine - and in particular for personalized medicine - can and will be found. California is in a particularly strong position, like no other region in the world, to be a leader in precisely this emerging field, stem cell genomics. Both sides of the equation are already in place and each field in its own right is a strong as only in a few other places. In particular genomics should be as strong as nowhere else in the world since all the components are concentrated in California, for example in Silicon Valley. However, for historic reasons there is for example no very large genome sequencing center in California. Personalized stem cell genomics could quite possibly be the key ingredient that makes personalized medicine become a full reality and move into profitable translational applications and into the clinic and it is important for California to make sure that both halves of the emerging field are strongly represented and supported so that the state can be at the very forefront of this development.