title: Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts.
abstract: BACKGROUND
  Human induced pluripotent stem (iPS) cells are currently used as powerful resources in regenerative medicine. During very early developmental stages, DNA methylation decreases to an overall low level at the blastocyst stage, from which embryonic stem cells are derived. Therefore, pluripotent stem cells, such as ES and iPS cells, are considered to have hypo-methylated status compared to differentiated cells. However, epigenetic mechanisms of "stemness" remain unknown in iPS cells derived from extra-embryonic and embryonic cells.
  
  
  RESULTS
  We examined genome-wide DNA methylation (24,949 CpG sites covering 1,3862 genes, mostly selected from promoter regions) with six human iPS cell lines derived from human amniotic cells and fetal lung fibroblasts as well as two human ES cell lines, and eight human differentiated cell lines using Illumina's Infinium HumanMethylation27. A considerable fraction (807 sites) exhibited a distinct difference in the methylation level between the iPS/ES cells and differentiated cells, with 87.6% hyper-methylation seen in iPS/ES cells. However, a limited fraction of CpG sites with hypo-methylation was found in promoters of genes encoding transcription factors. Thus, a group of genes becomes active through a decrease of methylation in their promoters. Twenty-three genes including SOX15, SALL4, TDGF1, PPP1R16B and SOX10 as well as POU5F1 were defined as genes with hypo-methylated SS-DMR (Stem cell-Specific Differentially Methylated Region) and highly expression in iPS/ES cells.
  
  
  CONCLUSIONS
  We show that DNA methylation profile of human amniotic iPS cells as well as fibroblast iPS cells, and defined the SS-DMRs. Knowledge of epigenetic information across iPS cells derived from different cell types can be used as a signature for "stemness" and may allow us to screen for optimum iPS/ES cells and to validate and monitor iPS/ES cell derivatives for human therapeutic applications.
authors.affiliation: Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nishino
authors.forename: Masashi
authors.initials: M
authors.lastname: Toyoda
authors.forename: Mayu
authors.initials: M
authors.lastname: Yamazaki-Inoue
authors.forename: Hatsune
authors.initials: H
authors.lastname: Makino
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukawatase
authors.forename: Emi
authors.initials: E
authors.lastname: Chikazawa
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyagawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akutsu
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
mesh_terms: D000650:Amnion / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors