Do paraxial mesoderm progenitor cells exist in the early embryo?
The primitive streak of the embryo functions as a posteriorly positioned growth zone. It has been suggested that a progenitor cell population resident within the primitive streak of the mouse embryo gives rise to the cells of the paraxial mesoderm. Future work will investigate the presence of such a stem or progenitor cell population using complementary approaches.
These methods will be used to establish the presence, identify the location and understand the behavior of paraxial mesoderm progenitors within the primitive streak. Furthermore we will investigate if the specification, behavior, survival or proliferation of these cells is regulated by Wnt signaling and/or T-box function.
Investigating the reprogramming of somatic nuclei.
Embryonic Stem (ES) cells are pluripotent cells derived from the mammalian balstocyst that have the capacity to give rise to any fetal tissue. The ES genome can be modified at base pair resolution. These two properties of mouse ES cells hold the promise of human ES cells for tissue replacement therapies. However, tissue rejection in an outbred population like humans precludes such hopes whereby each individual would require "custom" ES cells.
In recent years, nuclear transfer technology has renewed interest in using ES cells for cell-based therapies. In the mouse, if somatic cell nuclei are transferred to enucleated oocytes, then development of the oocyte can be fostered until at least blastocyst stage. Blastocysts can then be used to derive ES cells with nuclei of somatic cell origin. This nuclear transfer technology circumvents the problem of tissue rejection in outbred human populations, but generates two ethical concerns, that this technique would require: (i) the isolation of human oocytes on a large scale, and (ii) that human embryogenesis be initiated in vitro and arrested at blastocyst stage. Recently, these two ethical problems have been circumvented with the finding that both mouse and human ES cells, like enucleated oocytes, can reprogram somatic nuclei into an ES-like state. A better understanding of the reprogramming capacity of ES cells could allow for the production of "custom" ES cells for any given individual.
In collaboration with Dr Paul Feinstein at Rockefeller University we are investigating the reprogramming capacity of mouse ES cells on somatic cell types. We will determine the rate of reprogramming in vivo and establish whether somatically-derived ES cells are pluripotent.
