Human development is in general slower than mouse development, …but why? To study the mechanism of interspecies differences in developmental time scale, we recapitulate developmental processes in vitro through making organoids from pluripotent stem cells. The in vitro tissues offer an ideal platform to compare different species under the same experimental conditions. As a model system of interspecies differences, we have focused on the segmentation clock: the oscillatory gene expression that regulates the timing of somite formation during embryogenesis. Interestingly, the oscillation period of the human segmentation clock is approximately 5 hours, while that of mice is approximately 2 hours (Figure 1). We have found that several biochemical reactions of the segmentation clock are slower in human cells as compared with mouse cells. To expand the research, we are now exploring other organoids that display inter-species differences. We are also working on several mammalian species, including rabbits, cattle and rhinoceroses, setting up a ‘stem cell zoo’ in the lab.
In parallel, we develop genetic tools to manipulate organoids, as in vitro tissues are amenable to quantitative measurements and manipulation. We have recently developed an optogenetic tool to induce apical constriction in mammalian cells. Optogenetic manipulation of apical constriction caused several types of tissue deformation, including neuroepithelial thickening and apical lumen shrinkage of neural organoids (Figure 2). By manipulating the shape of organoids, we are now investigating the interplay between tissue shape and function.