Controlling Heterogeneity within Multicellular Populations

As evolution guided the development of multicellular animals by uniting unicellular organisms, single cells have had to adapt their social interactions and engage in mainly co-operative relationships with their neighbours. Nevertheless, remnants of natural selection and competition have remained an innate component of cell-cell interactions and govern the dynamics of cell populations. In the era of cellular engineering, where scientists can direct cell behaviour by engineering gene regulatory networks, cell competition remains an unexplored parameter by which we may be able to control population dynamics. Perhaps the most prominent example of cellular engineering is the recent discovery of induced pluripotent stem cells (iPSCs) in a process called reprogramming – a discovery which was recognized with a Nobel Prize in 2012. iPSCs provide an interesting model system in which to probe the impact of key transcription factors (TFs) on cell competition outcomes. In this talk, I will explore cell competition dynamics in reprogramming populations, utilizing a combined cellular barcoding, mathematical modelling, and lineage tracing approach. I will also discuss ongoing efforts towards constructing a feedback-mediated synthetic genetic circuit for tunable control of TF overexpression, enabling precise control over the reprogramming trajectory of cells while eliminating sources of heterogeneity.