Schwamborn

Project title: Function of cell fate determinants during acquisition and loss of pluripotency.

Embryonic stem cells (ESCs), which are derived from the inner cell mass of mammalian blastocysts, have the ability to grow indefinitely while maintaining pluripotency and the ability to differentiate into cells of all three germ layers. Recent pioneering experiments have shown that by expressing four selected factors pluripotent cells can be generated from adult somatic cells. These cells are called induced pluripotent stem (iPS) cells. Interestingly, besides knowing which factors are necessary to achieve the reprogramming, it is rather unknown what molecular mechanisms regulate the “reprogrammability” of a somatic cell into an iPS cell. Furthermore, also the mechanisms and molecules that mediate the exit from pluripotency are poorly understood. Because both processes, reprogramming into iPS cells and exit from pluripotency, represent changes in cell fate we propose the model that cell fate determinants are important regulators of these processes. Accordingly low levels of differentiation inducing cell fate determinants increase the potential of a cell to be reprogrammed into an induced pluripotent stem cell (iPS cell). In contrast the exit from pluripotency could be mediated by an upregulation of such determinants.
The successful completion of this project will lead to a more detailed understanding of the molecular mechanisms that regulate the entry and the exit into and from pluripotency.  Additionally, this project could lead to methods to make induction of pluripotency as well as directed differentiation of pluripotent cells more efficient.

Pluripotent stem cells (like ESCs or iPSCs) have the potential to differentiate into multipotent somatic stem cells (like NSCs). Those somatic stem cells can only give rise to certain tissue specific cell types. Neural stem cells for example are able to produce the terminally differentiated cell types Astrocytes, Oligodendrocytes and Neurons.

Probably low levels of differentiation inducing cell fate determinants increase the potential of a cell to be a pluripotent stem cell. In contrast the exit from pluripotency could be mediated by an upregulation of those differentiation inducing cell fate determinants.