Human iPSCs represent a potentially unlimited source of cells in regenerative medicine. However, we need to develop methods to differentiate iPSCs into mature and functional cell types. For example, if we could make mature liver cells from iPSCs, these could be used to treat patients with liver failure, who are currently on very long donor waitlists. Here, we developed new technologies to screen for conditions that promoted liver cell generation from iPSCs. We identified an extracellular matrix protein, Laminin411, as an important factor promoting iPSC-derived liver production.