Controlling the specific differentiation of stem cells (SCs) is a goal sought by many because of the benefits it would yield for repair or replacement of damaged tissues and organs. We report the discovery of signaling complexes and describe their use in predictably guiding the differentiation of mouse and human SCs. The signaling complexes (Signal-plexes^™ [S-ps]) induce mouse and human SCs to express specific phenotypes. The S-ps have been used to identify a new source of human SCs (Hu abba-1^™) and have been shown to induce differentiation of multiple tissue-specific phenotypes selectively in mouse pluripotent embryonic cells as well as in Hu abba-1 cells. Endocrine and exocrine pancreas, liver, lung, kidney, heart, cartilage, bone, and other cell types have been induced in SCs by S-ps, as shown by morphology, immunostaining, enzyme-linked immunosorbent assay, and reverse transcriptase–polymerase chain reaction analysis.