defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts

Koichiro Nishino, Masashi Toyoda, Mayu Yamazaki-Inoue, Hatsune Makino, Yoshihiro Fukawatase, Emi Chikazawa, Yoriko Takahashi, Yoshitaka Miyagawa, Hajime Okita, Nobutaka Kiyokawa, Hidenori Akutsu, Akihiro Umezawa

Research output: Contribution to journalArticle

37 Citations (Scopus)

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. Methodology/Principal Findings: 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/Significance: 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.

Original languageEnglish
Article numbere13017
JournalPLoS One
Volume5
Issue number9
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

amnion
Induced Pluripotent Stem Cells
Amnion
Fibroblasts
Stem cells
fibroblasts
stem cells
Stem Cells
lungs
promoter regions
Lung
Methylation
methylation
DNA methylation
DNA Methylation
Genes
human cell lines
genes
Epigenomics
epigenetics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Nishino, K., Toyoda, M., Yamazaki-Inoue, M., Makino, H., Fukawatase, Y., Chikazawa, E., ... Umezawa, A. (2010). defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts. PLoS One, 5(9), [e13017]. https://doi.org/10.1371/journal.pone.0013017

defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts. / Nishino, Koichiro; Toyoda, Masashi; Yamazaki-Inoue, Mayu; Makino, Hatsune; Fukawatase, Yoshihiro; Chikazawa, Emi; Takahashi, Yoriko; Miyagawa, Yoshitaka; Okita, Hajime; Kiyokawa, Nobutaka; Akutsu, Hidenori; Umezawa, Akihiro.

In: PLoS One, Vol. 5, No. 9, e13017, 2010.

Research output: Contribution to journalArticle

Nishino, K, Toyoda, M, Yamazaki-Inoue, M, Makino, H, Fukawatase, Y, Chikazawa, E, Takahashi, Y, Miyagawa, Y, Okita, H, Kiyokawa, N, Akutsu, H & Umezawa, A 2010, 'defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts', PLoS One, vol. 5, no. 9, e13017. https://doi.org/10.1371/journal.pone.0013017
Nishino, Koichiro ; Toyoda, Masashi ; Yamazaki-Inoue, Mayu ; Makino, Hatsune ; Fukawatase, Yoshihiro ; Chikazawa, Emi ; Takahashi, Yoriko ; Miyagawa, Yoshitaka ; Okita, Hajime ; Kiyokawa, Nobutaka ; Akutsu, Hidenori ; Umezawa, Akihiro. / defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts. In: PLoS One. 2010 ; Vol. 5, No. 9.
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AU - Makino, Hatsune

AU - Fukawatase, Yoshihiro

AU - Chikazawa, Emi

AU - Takahashi, Yoriko

AU - Miyagawa, Yoshitaka

AU - Okita, Hajime

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