title: Promotion of hematopoietic differentiation from mouse induced pluripotent stem cells by transient HoxB4 transduction.
abstract: Ectopic expression of HoxB4 in embryonic stem (ES) cells leads to an efficient production of hematopoietic cells, including hematopoietic stem/progenitor cells. Previous studies have utilized a constitutive HoxB4 expression system or tetracycline-regulated HoxB4 expression system to induce hematopoietic cells from ES cells. However, these methods cannot be applied therapeutically due to the risk of transgenes being integrated into the host genome. Here, we report the promotion of hematopoietic differentiation from mouse ES cells and induced pluripotent stem (iPS) cells by transient HoxB4 expression using an adenovirus (Ad) vector. Ad vector could mediate efficient HoxB4 expression in ES cell-derived embryoid bodies (ES-EBs) and iPS-EBs, and its expression was decreased during cultivation, showing that Ad vector transduction was transient. A colony-forming assay revealed that the number of hematopoietic progenitor cells with colony-forming potential in HoxB4-transduced cells was significantly increased in comparison with that in non-transduced cells or LacZ-transduced cells. HoxB4-transduced cells also showed more efficient generation of CD41-, CD45-, or Sca-1-positive cells than control cells. These results indicate that transient, but not constitutive, HoxB4 expression is sufficient to augment the hematopoietic differentiation of ES and iPS cells, and that our method would be useful for clinical applications, such as cell transplantation therapy.
authors: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors: Katsuhisa
authors: K
authors: Tashiro
authors: Kenji
authors: K
authors: Kawabata
authors: Miyuki
authors: M
authors: Omori
authors: Tomoko
authors: T
authors: Yamaguchi
authors: Fuminori
authors: F
authors: Sakurai
authors: Kazufumi
authors: K
authors: Katayama
authors: Takao
authors: T
authors: Hayakawa
authors: Hiroyuki
authors: H
authors: Mizuguchi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D014157:Transcription Factors / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors