Researchers have published the first systematic analysis of the effects of various inducing factors on embryonic stem (ES) cell differentiation (PNAS 97, 11307–11312, 2000). The work represents an important step toward efforts to direct ES cell differentiation toward specific cell types (e.g., insulin-producing pancreatic β-cells) for cell replacement therapies. To achieve their aim, Douglas Melton and his colleagues first tested ES cells for the expression of eight inducing factor receptors to ensure the pluripotency of ES cells in five-day old embryoid bodies (EBs). The EBs were then treated with the eight inducing factors and grown for 10 days. When the cells were assayed for 24 cell-specific genes to determine the resulting germ cell layer inductions, none of the growth factors directed differentiation exclusively to one cell type, and the researchers concluded that inducing factors both inhibit and induce differentiation of specific cell types, with a complex combination of possibly hundreds of inducing factors required for complete cell specialization. Currently, knowledge on the pathways of stem cell differentiation signaling is very limited: “This work shows how to approach the problem,” says Melton.