title: In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2.
abstract: 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 multilineage 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.
authors.affiliation: Stem Cell Project Group, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan. kitajima-kj@igakuken.or.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitajima
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Minehata
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D016466:CHO Cells; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014162:Transfection
chemical_list: D000950:Antigens, Ly; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit