Genomics is the study of all the DNA in a cell. That includes the actual sequence of the DNA, which is the same in all the cells of a person’s body, as well as the molecular decorations hanging on to the DNA. Those decorations, collectively called epigenetics, can determine the behavior of the genes such as which are active or inactive in a given cell. It’s epigenetics that can control why, if a hair cell and a liver cell have the same DNA, one makes hair and the other makes liver enzymes. Those epigenetic changes are also responsible for why an embryonic stem cell behaves one way, and the neuron it can mature into behaves differently.
Genomics also reveals molecules called RNA that are coded by the DNA and controlled by epigenetics. RNA can reveal a cell’s status as it differs from cell to cell depending on what kind of cell it is and whether the cell is healthy, diseased, or in damaged tissue.
Here are a few examples of how genomics is important for stem cell research. Let’s say a team wants to create reprogrammed iPS cells from the skin of a person with a genetic disease like Parkinson’s disease. First, those researchers need to know whether the process of reprogramming that skin cell into an embryonic-like cell altered the DNA. There’s a lot of controversy over whether iPS cells truly mimic embryonic stem cells (which we blogged about here), and knowing more about the genomics of iPS cells will help develop the best methods for creating those cells. This will also help the CIRM’s cell banking initiative, which will fund researchers to create and bank iPS cells in addition to banking embryonic stem cells for widespread distribution to stem cell researchers. With access to genomics resources we can be sure those iPS cells are genetically normal and consistent.
If we want to study and treat Parkinson’s disease, the next step would be to mature those iPS cells into dopaminergic neurons ,the type of neuron that goes awry in the disease. Genomic analysis will tell researchers whether the dopaminergic neurons are different when they are generated from skin cells of people without the disease and from people with the disease. Those differences could reveal a lot about what causes the disease in the first place. The information can also be used to screen for drugs that make neurons from people with the disease more like their normal, non-diseased counterparts.
The information is incredibly powerful. It’s also growing much, much cheaper. In the past it was too expensive and time-consuming to routinely carry out genomic analysis. With those costs coming down, and the process speeding up, it’s a good time to invest in genomics resources that would be available to California researchers.
In a paper published this month in Nature Biotechnology, CIRM president Alan Trounson with Natalie DeWitt and Michael Yaffe of the science office wrote:
For California to take a firm and lasting grip on leadership in stem-cell research—and, as stated in Proposition 71, “advance the biotech industry in California to world leadership as an economic engine for California's future”—its scientists must have access to these technologies and moreover create a coordinated international enterprise to maximize the reach and impact of stem cell genomics. Genomics is creating a sea change in biomedical research and medicine, and accordingly, the California Institute for Regenerative Medicine (CIRM; San Francisco) can create a process through which stem-cell research can participate and even provide leadership in a new era of medicine… With judicious expenditure of CIRM funds, it should be possible to use existing resources to rapidly and efficiently build an effective stem-cell genomics infrastructure that will be unique in the world, thus positioning California as a leader in this critical area of basic and translational research while genomic technologies build steam in the next five years.The group also points out that although several research institutes in other states provide comprehensive genomics centers, none exist in California. That’s despite the fact that several of the major companies that make genomics tools are located in the state.
The requests for applications (RFA) for this initiative will be posted on this page of the CIRM website this spring. If you haven’t already signed up, here’s a link where you can sign up to get an email alert whenever CIRM posts a new RFA.
Dewitt ND, Yaffe MP, & Trounson A (2012). Building stem-cell genomics in California and beyond. Nature biotechnology, 30 (1), 20-5 PMID: 22231086