Human embryonic stem cells (hESCs) have the potential to proliferate indefinitely when maintained undifferentiated in culture, and to differentiate to basically all functional cell types. The molecular mechanisms underlying these biological processes in hE SCs are not well characterized. To maintain these cells undifferentiated in culture they can be cultured on an extra-cellular matrix in the presence of conditioned medium from mouse embryo fibroblasts (MEFs) and fibroblast growth factor-2 (FGF-2). This sugg ests that MEFs produce a factor/s that is/are required for the maintenance of undifferentiated state of hESCs. Further analysis has revealed that treatment of the MEFs with FGF-2 is involved in the production of these factors. A global expression profile analysis using micro-arrays between MEFs treated without or with FGF-2 indicated that around 20 secreted factors are down regulated in the absence of FGF-2. These factors included several ligands for known signaling pathways as well as extra-celluar proteases, which in turn can be involved in the processing of ligands, and components of the extra-cellular matrix, which in turn can be involved in cells matrix interaction and subsequent signalling events. The identification of these factors and the availability of ESTs harbouring their genes will allow us to identify factors required for the undifferentiated state of hESCs and their downstream signalling events. Moreover we have recently shown, that activation of the Activin/Nodal signalling pathway and subsequent activation of the transcription factors Smad2/3 are important for the maintenance of the undifferentiated state. The interaction of the regulation of the Activin/Nodal pathway and the factors secreted by the MEFs upon FGF-2 treatment will reveal important mechanisms that underlie the maintenance of the undifferentiated state of hESCs and will have a major impact in the knowledge of the biology of these cells.
Field of science
- /medical and health sciences/medical biotechnology/cells technologies/stem cells
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