Gene Regulation

——

What interactions among transcription factors drive cell differentiation from pluripotency to terminal differentiation?

Our goal is to understand all transcription factor (TF) required for every mammalian lineage, which is undoubtedly ambitious, but we charted a clear path to begin. We use different strategies to solve puzzles at home, depending on whether we have 80 or 10 percent of the pieces. So, we recently asked ourselves: how many pieces of this TF puzzle do we have? The field has identified around 30 TFs while we counted around ~600 TFs transcribed during motor neuron differentiation. Now we are aware of what we do not know. We developed a system to functionally identify and study all the TFs required for any mammalian lineage, whether differentiated from adult or pluripotent stem cells. The emerging theme in our research is the mostly uncharacterized zinc finger TF family, the largest family in our genome but the least studied. We have opened a window to analyze all TFs in all cell types: every TF, every cell.