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

阐明人胚胎干细胞（ES）和诱导多能干细胞（iPS）的体外分化对于理解正常和病理性造血发育具有重要意义。为此，需要一种可靠、简单的造血分化系统，能够准确地追踪体内造血。在这项研究中，我们建立了一种新的无血清单层培养，可以追踪从ES/iPS细胞到功能明确的血细胞通过中胚层祖细胞的体内造血途径。外源性细胞因子混合物通过原条细胞诱导造血中胚层祖细胞。这些祖细胞然后分化成各种细胞谱系取决于造血细胞因子的存在。此外，单细胞沉积实验显示，在我们的培养物中诱导了常见的双能血管生成祖细胞。我们的系统提供了一个新的，强大的，和简单的方法来研究themodermal和造血分化的机制。

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.