Signals from the Surface to Promote Human Pluripotent Stem Cell Differentiation

Human pluripotent stem cells (human embryonic stem cells and induced pluripotent stem cells) have the ability to self-renew indefinitely and differentiate into specialized types. Soluble signals (e.g., growth factors or small molecules) have been identified that promote human pluripotent stem (hPS) cell differentiation. Most standard differentiation protocols employ Matrigel, an undefined and complex mixture of over 1800 proteins. The role of the insoluble signals in directing differentiation is largely unexplored. To mine this molecular space, we devised arrays of chemically defined surfaces composed of self-assembled monolayers of peptides. Using the results from our array screen, we generated peptide-modified surfaces and used them to elucidate the molecular mechanisms by which insoluble signals guide hPS cell differentiation to each of the primary germ layers.  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. They also underscore the utility of defined surfaces to dissect critical signaling pathways.