Tracking the Dynamics of Metabolic Changes driving Early Human Development on Chip

Human embryonic development is a tightly regulated process in which mechanical, metabolic and biochemical cues drive cell fate specification and tissue organization. Recent work identified shifts in central carbon metabolism delineating naïve from primed cell states in pluripotent stem cells, as well as ties linking metabolic processes to chromatin during early differentiation. Thus, the ability to track changes in central carbon metabolism in real-time could highlight the dynamics of early human development.
In this work, we present human pluripotent stem cell-derived blastocyte on a chip. The blastocyte-like 3D aggregates express naïve markers and are embedded with oxygen microsensors allow us to track oxygen consumption using two-frequency phase modulation in real-time. Moreover, connecting an electrochemical sensor array to the output flow allows us to monitor glucose, lactate and glutamine fluxes. This model permits the calculation of dynamic changes in metabolic fluxes around central carbon metabolism during human potent stem cell transition between the naïve, primed and differentiated states. Our work provides a unique set of tools to study early human development, characterize new phenotypic states and define the dynamics of early differentiation events.