Human pluripotent stem cells (human embryonic stem cells and induced pluripotent stem cells) have two extraordinary properties. First, they can self-renew indefinitely, and second, they can differentiate into many different cell types. Coaxing them to either propagate or differentiate ex vivo is difficult, and most culture conditions are chemically undefined. Our goal is to discover chemically defined conditions to control human pluripotent stem cell self-renewal and differentiation. In physiological settings, the cues that direct stem cell self-renewal or differentiation come from the niche. The microenvironment of the niche transmits information through three types of components: soluble molecules, neighboring cells, and the collection of secreted proteins and glycans that is termed the extracellular matrix. In seeking conditions for human pluripotent stem cell culture and differentiation, researchers have focused identifying soluble components that influence cell decisions. We postulated that insoluble components also deliver signals that direct cell decisions. To this end, we have devised arrays chemically defined surfaces composed of self-assembled monolayers. From these arrays, we identified surfaces with surprising assets: They not only permit human pluripotent stem cells to differentiate to specific lineages but even instruct them to do so. Our findings highlight the dramatic effects of insoluble cues on stem cell pluripotency and differentiation.

Insoluble chemical cues that instruct human pluripotent stem cells

243rd National Meeting (2012)

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