Constructing a fate map of the human embryo
The United States government does not fund research involving human embryos or cells that were grown from them after August 9, 2001. In addition, other restrictions have been imposed that make these types of experiments extremely difficult to do. For example, work cannot be conducted alongside research that is funded by government agencies, the typical mode in which academic research laboratories operate. In practical terms, this means that duplicate facilities must be created to do the large amount of research that is needed to turn human embryonic stem cells (hESCs) into robust experimental tools that will enable us to understand disease processes, the first step in curing them. These onerous regulations, unprecedented in our country, have stifled progress in this exciting new area of medical research. Thus, there is a great deal of basic work that remains to be accomplished. Our group is focusing on one particular area--the enigmatic process that occurs when an embryo--which would otherwise be discarded at the conclusion of an in vitro fertilization (IVF) treatment--is donated for research and grown in a laboratory. In certain cases, the cells that would have gone on to form specialized tissues such as blood cells, and major organs such as the heart and pancreas, continue to make copies of themselves. As first shown in 1998, the copies, termed hESC lines, may remember how to do their original job, i.e., differentiate into every type of cell in the human body. Scientists think that this is possible, because in many laboratory animals the equivalent populations retain this ability. Our group wants to optimize the methods that are used to make new hESC lines, because the techniques that are currently used are essentially random. Embryos are maintained in the laboratory until outgrowths--collections of cells that look very different from one another--appear. During this 2- to 3-week process, many of these cells die, but a subset start to make copies of themselves. Thus, much remains to be learned about the derivation process. For example, we do not know when, during this extended time period, the actual progenitor cell(s) arises, and it is unclear whether all the cells of the embryo are equally able to give rise to hESC lines. Thus, we propose to test the theory that there are better, more controlled ways to produce hESCs. Recently, our collaborators showed that it is possible to make lines from single cells that are removed from human embryos at a specific time. We want to use their method to determine if hESCs made from individual cells that are removed at different times from specific regions of the embryo are better equipped to generate all the cell types found in the body. Essentially, we want to harness and standardize the process of developing new lines. This work, which cannot be supported by the federal government, has important implications for devising hESC-based patient therapies.
University of California, San Francisco