論文

査読有り
2010年9月

Defining Hypo-Methylated Regions of Stem Cell-Specific Promoters in Human iPS Cells Derived from Extra-Embryonic Amnions and Lung Fibroblasts

PLOS ONE
  • 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
  • 全て表示

5
9
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0013017
出版者・発行元
PUBLIC LIBRARY SCIENCE

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.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0013017
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20885964
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000282167100018&DestApp=WOS_CPL
URL
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77958616286&origin=inward
ID情報
  • DOI : 10.1371/journal.pone.0013017
  • ISSN : 1932-6203
  • PubMed ID : 20885964
  • Web of Science ID : WOS:000282167100018

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