Gene Regulation

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

Our goal is to understand all the transcription factors (TFs) required for every mammalian lineage. While undoubtedly ambitious, we have charted a clear path to begin. Think about it like this, when solving a puzzle at home, your strategy changes depending on whether you have 80% or 10% of the pieces. So, we recently asked ourselves: how many pieces of this TF puzzle do we have? While the field has only identified around 50 TFs, we have counted around 800 TFs transcribed during motor neuron differentiation. So what are these TFs? Are they required for cell differentiation? If so, which TFs are required for which mammalian lineages? To answer these questions, we have 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 involvement of the mostly uncharacterized zinc finger TF family, the largest family in our genome but the least studied.

Through our work we have opened a window to analyze all TFs in all cell types: every TF, every cell.