title: Activation of OCT4 enhances ex vivo expansion of human cord blood hematopoietic stem and progenitor cells by regulating HOXB4 expression.
abstract: Although hematopoietic stem cells (HSC) are the best characterized and the most clinically used adult stem cells, efforts are still needed to understand how to best ex vivo expand these cells. Here we present our unexpected finding that OCT4 is involved in the enhancement of cytokine-induced expansion capabilities of human cord blood (CB) HSC. Activation of OCT4 by Oct4-activating compound 1 (OAC1) in CB CD34(+) cells enhanced ex vivo expansion of HSC, as determined by a rigorously defined set of markers for human HSC, and in vivo short-term and long-term repopulating ability in NSG mice. Limiting dilution analysis revealed that OAC1 treatment resulted in 3.5-fold increase in the number of SCID repopulating cells (SRCs) compared with that in day 0 uncultured CD34(+) cells and 6.3-fold increase compared with that in cells treated with control vehicle. Hematopoietic progenitor cells, as assessed by in vitro colony formation, were also enhanced. Furthermore, we showed that OAC1 treatment led to OCT4-mediated upregulation of HOXB4. Consistently, siRNA-mediated knockdown of HOXB4 expression suppressed effects of OAC1 on ex vivo expansion of HSC. Our study has identified the OCT4-HOXB4 axis in ex vivo expansion of human CB HSC.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.|Soonchunhyang Institute of Medi-bio Science, Chungcheongnam-do, Korea.
authors.forename: M-R
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cooper
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: G
authors.initials: G
authors.lastname: Hangoc
authors.affiliation: Konkuk University School of Medicine, Seoul, Korea.
authors.forename: K-S
authors.initials: KS
authors.lastname: Hong
authors.affiliation: Konkuk University School of Medicine, Seoul, Korea.
authors.forename: H-M
authors.initials: HM
authors.lastname: Chung
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Broxmeyer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D014157:Transcription Factors