title: SALL4 is a key transcription regulator in normal human hematopoiesis.
abstract: BACKGROUND
  Stem cell factor SALL4 is a zinc finger transcription factor. It plays vital roles in the maintenance of embryonic stem cell properties, functions as an oncogene in leukemia, and has been recently proposed to use for cord blood expansion. The mechanism(s) by which SALL4 functions in normal human hematopoiesis, including identification of its target genes, still need to be explored.
  
  
  METHODS
  Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) was used for mapping SALL4 global gene targets in normal primary CD34+ cells. The results were then correlated with SALL4 functional studies in the CD34+ cells.
  
  
  RESULTS
  More than 1000 potential SALL4 downstream target genes have been identified, and validation of binding by ChIP-quantitative polymerase chain reaction was performed for 5% of potential targets. These include genes that are involving in hematopoietic differentiation and self-renewal, such as HOXA9, RUNX1, CD34, and PTEN. Down regulation of SALL4 expression using small-hairpin RNA in these cells led to decreased in vitro myeloid colony-forming abilities and impaired in vivo engraftment. Furthermore, HOXA9 was identified to be a major SALL4 target in normal human hematopoiesis and the loss of either SALL4 or HOXA9 expression in CD34+ cells shared a similar phenotype.
  
  
  CONCLUSIONS
  Taken together, SALL4 is a key regulator in normal human hematopoiesis and the mechanism of its function is at least in part through the HOXA9. Future study will determine whether modulating the SALL4/HOXA9 pathway can be used in cellular therapy such as cord blood expansion and/or myeloid engraftment.
authors.affiliation: Department of Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Gao
authors.forename: Nikki R
authors.initials: NR
authors.lastname: Kong
authors.forename: Ailing
authors.initials: A
authors.lastname: Li
authors.forename: Hiro
authors.initials: H
authors.lastname: Tatetu
authors.forename: Shikiko
authors.initials: S
authors.lastname: Ueno
authors.forename: Youyang
authors.initials: Y
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Jianchang
authors.initials: J
authors.lastname: Yang
authors.forename: Yupo
authors.initials: Y
authors.lastname: Ma
authors.forename: Grace S
authors.initials: GS
authors.lastname: Kao
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
authors.forename: Li
authors.initials: L
authors.lastname: Chai
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D018398:Homeodomain Proteins; C472575:SALL4 protein, human; D014157:Transcription Factors; C097899:homeobox protein HOXA9