Paracrine en transcriptionele regulatie van zelfvernieuwing en differentiatie van embryonale en adulte multi-potente progenitor cellen in vertebraten.

The combined insights gained from developmental biology and stem cell (de)differentiation studies will be needed to create successful cell-based therapies. However, the derivation of fully funtional therapeutic cells that differentiate from stem/progenitor cells is much more complex than previously expected. For example, instructions to stem/progenitor cell cultures in an attempt to mimic what happens in vivo during normal development can still only be recreated in part, thereby preventing further progress of the field. Indeed, it is difficult to mimic in cell culture or in current bio-artificial tissues the spatial organization of cells and their stepwise differentiation under the determining influence of cell-cell and cell-matrix interactions. In order to close the gap between the in vitro stem cell systems and the in vivo conditions, there is a need to study the regulation of cell renewal, pluripotency and differentiation in the early embryo and test these findings in stem cell culture systems. This OT project is a first step towards the critical combination of the types of expertise mentioned above and brings together 4 partners with complementary expertise, ranging from growth factor signaling and resulting transcriptional and epigenetic regulation in the mouse embryo and its ESCs as well as in postnatal stem/progenitor cells derived from mice, leading to differentiation into neuroextodermal, mesodermal or endodermal cell types, to the validation of some of these stem cells in tissue repair in vivo.

Trefwoorden:Embryo, Progenitor cells