Abstract

Organoids as Emergent Systems Inducible by Designing the Adhesion Microenvironment of Stem Cells

Kennedy Okeyo, Senior Lecturer, Institute for Frontier Life and Medical Sciences, Kyoto University

The adhesion microenvironment plays important contributory roles in the induction of self-organized tissue formation and differentiation of pluripotent stem cells (PSCs). However, how the interaction with the surrounding physical microenvironment influences the complex processes of self-organization and differentiation which orchestrate organoid formation by stem cells remains to be fully understood. In this research, we are examining how the local adhesion microenvironment, as characterized by both cell-substrate and cell-cell adhesions, can trigger self-organization and differentiation globally, and lead to the emergence of higher-order structures such as organoids from lower-order cellular systems. To this end, we have developed a simple but versatile culture platform, namely, the micromesh culture technique which employs adhesion-limiting microstructured mesh substrates to modulate adhesion microenvironment and trigger self-organization of stem cells into ordered 3D structures in a manner which mimics tissue morphogenesis. This talk will highlight our recent findings that modulating the cell adhesion microenvironment by our culture technique can potentially trigger stem cells to exhibit differentiation and self-organization as seen in early embryogenesis, such as the emergence of the trophectoderm and primordial germ cells (PGCs), even under pluripotency maintaining culture conditions in vitro.