Induction of hematopoietic stem/progenitor cells and functional blood cells from human ES/iPS cells

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Elucidating the in vitro differentiation of human embryonic stem(ES) and induced pluripotent stem(iPS) cells is important for understanding both normal and pathological hematopoietic development invivo. For this purpose, a robust and simple hematopoietic differentiation system that can faithfullytrace in vivo hematopoiesis is necessary. In this study, we established a novel serum-free monolayerculture that can trace the in vivo hematopoietic pathway from ES/iPS cells to functional definitiveblood cells via mesodermal progenitors. Stepwise tuning of exogenous cytokine cocktails induced thehematopoietic mesodermal progenitors via primitive streak cells. These progenitors were thendifferentiated into various cell lineages depending on the hematopoietic cytokines present. Moreover, single cell deposition assay revealed that common bipotential hemoangiogenic progenitors wereinduced in our culture. Our system provides a new, robust, and simple method for investigating themechanisms of mesodermal and hematopoietic differentiation.