Prevalence and functional consequences of chromosomal mosaicism in hESC lines.
Human embryonic stem cells (hESCs) hold great promise for treating many human diseases because of their ability to become any type of cell in the human body. In order to choose the optimal hESCs for therapeutic use in various diseases, it is critical to
characterize fully the safety and potential of different stem cell lines. Chromosomes are large packages of DNA within a cell, and changes to a cell’s chromosomes can affect its function. Large scale chromosome changes include: the loss and gain of whole chromosomes, termed aneuploidy; partial loss of chromosomes, deletion; and movement of large chromosome segments between chromosomes, translocation.
As chromosomal changes can dramatically alter the properties of many cell types, it is important to assess and compare the prevalence and consequences of chromosomal changes in hESC lines. Our proposed research will use a technique that fluorescently labels each chromosome pair within a cell with a unique color, to allow us to identify aneuploidy, deletions and translocations within stem cells. We will further observe whether extended culture time in the laboratory can influence the characteristics of chromosomes within stem cells.
Once we know what changes are occurring at the chromosome level within a stem cell population, it is crucial to determine how these changes affect their capacity to become different cell types, including normal and/or tumor cells. The second part of our proposal will compare the ability of stem cell populations with or without chromosome changes, to survive, divide and become neurons. The data gained from this proposal will provide key information for future stem cell research regarding the therapeutic potential and safety of hESCs.
The California Institute of Regenerative Medicine will be funding many research projects designed to use human embryonic stem cells for treating many human diseases, including Parkinson’s and Alzheimer’s diseases, diabetes and cancer. Clearly this research will benefit the lives of hundreds of thousands of Californians who are affected by these diseases, if it leads to safe and effective treatments. However, in order to spend California’s limited research dollars on the most promising research, it is vital to know which stem cell lines have the best therapeutic potential. Our proposal addresses this key issue through assessing genetic changes at the chromosome level that can influence the function and survival of different stem cell populations.
Strong California-based expertise in the hESC field will attract biotechnology industries and top academic researchers to the area, bringing more jobs and money into the state of California. San Diego is currently a hotbed for stem cell research with multiple research institutions that have dedicated stem cell research programs, including The Scripps Research Institute and The Burnham Research Institute. The collaborative nature of our research proposal will foster high quality stem cell research in this region that is based on a clear understanding of the basic genomic characteristics of the cells being studied.