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Blood First Edition Paper, prepublished online February 22, 2011; DOI 10.1182/blood-2010-07-298596.
& l- n H5 Z, X' P U4 l6 a1 h7 g) QSubmitted July 27, 2010; accepted January 26, 2011.- v/ h3 u9 ^0 K7 K
http://bloodjournal.hematologyli ... ;resourcetype=HWCIT, W' H3 f) w: w' a
In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2Kenji Kitajima1,*, Ken-ichi Minehata1, Kenji Sakimura2, Toru Nakano3 and Takahiko Hara1
* G% T! e% P+ J1 Stem Cell Project group, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan; 2 Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan; 3 Department of Stem Cell Pathology, Medical School and Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
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* Corresponding author; email: kitajima-kj@igakuken.or.jp 2 V+ a* n! A8 z, F
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Abstract3 u. G. H1 Q0 r% F: p
Identification of genes involved in in vitro differentiation induction of embryonic stem cells (ESCs) into hematopoietic stem cells (HSCs) has been challenged during last decade. To date, a homeobox transcription factor Hoxb4 has been only demonstrated to possess such an effect in mice. Here, we show that HSC-like cells were efficiently induced from mouse ESCs by enforced expression of Lhx2, a LIM-homeobox transcription factor. Transduction of Lhx2 into ESC-derived mesodermal cells resulted in robust differentiation of c-Kit+/Sca-1+/Lineage- (KSL) cells in vitro. The KSL cell induction frequency was superior to the case of Hoxb4. Furthermore, transplantation of Lhx2-transduced hematopoietic cells into lethally irradiated mice resulted in multi-lineage repopulation of hematopoietic cells over 4 months. Transduction of Lhx2 into induced pluripotent stem cells (iPSCs) was also effective in generating KSL cells in vitro, as well as HSC-like activities in vivo. These results demonstrate that ectopic expression of Lhx2 confers an in vivo engrafting capacity to ESC/iPSC-derived hematopoietic cells and in vivo behavior of iPSC-derived hematopoietic cells is almost identical to that of ESC-derived cells.
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