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Orderly hematopoietic development of induced pluripotent stem cells via Flk‐1 + hemoangiogenic progenitors
Author(s) -
Niwa Akira,
Umeda Katsutsugu,
Chang Hsi,
Saito Megumu,
Okita Keisuke,
Takahashi Kazutoshi,
Nakagawa Masato,
Yamanaka Shinya,
Nakahata Tatsutoshi,
Heike Toshio
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21864
Subject(s) - biology , induced pluripotent stem cell , microbiology and biotechnology , haematopoiesis , embryonic stem cell , endothelial stem cell , stem cell , progenitor cell , somatic cell , cellular differentiation , stromal cell , induced stem cells , adult stem cell , cell potency , genetics , in vitro , cancer research , gene
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.