Embryonic stem cell differentiation
A new project will use embryonic stem cells (ESCs), which are immortal, and that develop normally after injection into an early embryo. The initial objective is to define procedures, in vitro, that differentiate ESCs into fully functional PHSCs. In theory, this should be easy, because ESCs readily differentiate to produce cells containing hemoglobin in vitro, and they pass through the stage where they function as PHSCs. (They may produce hemoglobin by an entirely novel pathway. This seems much less likely, although still interesting.) However, in the past, no one has gotten reproducible results using ESC descendants to function as PHSCs in vivo.
Our advantage is the use of the competitive repopulation assay to compare various ESC descendants with normal PHSCs. This assay precisely compares relative repopulating abilities, and we can compare about 20 different cell types in each experiment. This allows us to rapidly and effectively test hypotheses about growth factors and mechanisms of cell stimulation at the molecular level.
At The Jackson Laboratory, we also have the advantages of the availability of wide varieties of well-defined ESC lines and culture conditions, and the unique variety of mouse models available for in vivo studies. We have excellent collaborators: Barbara Knowles and Davor Solter, who are expert in the biology of ESC differentiation, and Jane Barker, who is the world leader in transplanting SCs, before birth, into embryos as young as 9–10 days old. Dr. Barker's work is important to us because the embryonic or fetal environment may be necessary to consistently support primitive ESC descendants.