Spatiotemporal models of mammalian development: An epigeneticist’s dream or nightmare?

My research group aims to address the fundamental challenge of understanding how multicellular organisms achieve variation despite cells having identical genetic information. The development of a single fertilized egg into a complete mammalian embryo is an especially beautiful embodiment of this problem. During this process, cellular differentiation is defined by the capacity of the cell ensemble to acquire increasingly more specialized internal states in a coordinated fashion. Our research program is based on the premise that a comprehensive quantitative model of mammalian development will necessitate the integration of three primary layers of phenomenological information: (i) The natural flux of cell state changes over time. (ii) The sum of extracellular cues affecting cell specification in the three-dimensional embryonic space in a non-cell-autonomous manner and (iii) epigenetic makeup shaping and memorizing cellular states cell-autonomously. We are excited by recent breakthroughs in single-cell transcriptomics and epigenomics since these can capture the emergence of embryonic cellular diversification at incredible resolution. But, we believe there is an urgent need in the field to match descriptive single cell atlases with models and experimental frameworks to derive novel understanding of function and regulation in this process. In my talk, I will present recent progress by my group towards these aims.