FGF2 and oxygen: Regulators of intergrin alpha-11 and extracellular matrix molecules

Recently, derivation and maintenance of pluripotent stem cells has been focused on environmental cues, with emphasis on the role of extracellular matrix (ECM) and adhesion molecules (AM). We have developed a novel approach that allows for induction of stem cell gene expression in human dermal fibroblasts (hDF) without the use of transgenes. By culturing cells in low oxygen (5% O₂) with addition of exogenous FGF2 we have shown that hDF in defined culture conditions express stem cell genes and show translation and nuclear translocation of stem cell transcription factors. We have demonstrated that this shift is coupled with an FGF2-dependent down-regulation of the majority of AM and ECM targets; specifically induction of a significant down-regulation of integrin alpha 11 (Itga11) transcript and results in Itga11 loss from focal adhesions. Investigation of the mechanism by which FGF2 may be involved in regulation of Itga11 is being investigated by studying the molecular pathway downstream of FGF2 ligand that may be involved in the loss of Itga11 and associated collagen I attachment. Dissecting the molecular mechanisms involved in regulation through modulation of extracellular environment and its effect on plasticity may provide insight into the acquisition into the mechanisms involved in reprogramming of differentiated cells.