Evolutionary ancient transcription factors: master keys to unlock lineage differentiation?

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Our body contains hundreds of different cell types. All these cells carry the same set of genetic instructions, but perform very different functions depending on which genes they decide to express. Therefore, control of gene expression is key to the identity (and function) of each cell. Gene expression is controlled by a class of proteins called transcription factors (TFs). It is well established that the generation of specific cell types requires the presence of certain TFs called lineage-specific TFs, exclusively restricted to a specific cell type or its progenitors. However, addition of a set of lineage-specific TFs is not sufficient to transform a cell into the cell type that normally contains that set, suggesting that further ingredients are required for differentiation. Our preliminary work indicates that a family of evolutionary ancient TFs, expressed in most cell types, function as master 'keys' to unlock cell differentiation. We will use state-of-the-art experimental technologies to understand how these regulators contribute to specific cells states and test if they can help lineage-specific TFs to achieve the desired cell types. The ability to reprogram endogenous fibroblasts into cell types of interest has important implications for regenerative medicine and disease modelling. Collectively, these results will provide new insight into how cell states are established, with direct relevance for generating specific cell types from stem cells or even from other adult cell types.