For many cell types, no specific cell-surface markers that would facilitate their isolation have been identified. In this study, Miki et al. describe a method to isolate specific cell types on the basis of their endogenous microRNA (miRNA) activity. The authors designed 'miRNA switches', which are synthetic mRNAs that encode fluorescent proteins and that contain a specific miRNA target site in their 5′ untranslated region. Cells expressing the corresponding endogenous miRNA can be distinguished from other cells as they induce the translational repression of the reporter. This method enabled the purification of specific cell types differentiated from human pluripotent stem cells, such as cardiomyocytes, hepatocytes, endothelial cells and insulin-producing cells.