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Orderly hematopoietic development of induced pluripotent stem cells via Flk-1+ hemoangiogenic progenitors

✍ Scribed by Akira Niwa; Katsutsugu Umeda; Hsi Chang; Megumu Saito; Keisuke Okita; Kazutoshi Takahashi; Masato Nakagawa; Shinya Yamanaka; Tatsutoshi Nakahata; Toshio Heike


Book ID
102882796
Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
723 KB
Volume
221
Category
Article
ISSN
0021-9541

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✦ Synopsis


Abstract

Induced pluripotent stem (iPS) cells, reprogrammed somatic cells with embryonic stem (ES) cell‐like characteristics, are generated by the introduction of combinations of specific transcription factors. Little is known about the differentiation of iPS cells in vitro. Here we demonstrate that murine iPS cells produce various hematopoietic cell lineages when incubated on a layer of OP9 stromal cells. During this differentiation, iPS cells went through an intermediate stage consisting of progenitor cells that were positive for the early mesodermal marker Flk‐1 and for the sequential expression of other genes that are associated with hematopoietic and endothelial development. Flk‐1^+^ cells differentiated into primitive and definitive hematopoietic cells, as well as into endothelial cells. Furthermore, Flk‐1^+^ populations contained common bilineage progenitors that could generate both hematopoietic and endothelial lineages from single cells. Our results demonstrate that iPS cell‐derived cells, like ES cells, can follow a similar hematopoietic route to that seen in normal embryogenesis. This finding highlights the potential use of iPS cells in clinical areas such as regenerative medicine, disease investigation, and drug screening. J. Cell. Physiol. 221: 367–377, 2009. © 2009 Wiley‐Liss, Inc.