Epigenetic status of H19/IGF2 and SNRPN imprinted genes in aborted and successfully derived embryonic stem cell lines in non-human primates

Stem Cell Res. 2016 May;16(3):557-67. doi: 10.1016/j.scr.2016.03.002. Epub 2016 Mar 9.


The imprinted genes of primate embryonic stem cells (ESCs) often show altered DNA methylation. It is unknown whether these alterations emerge while deriving the ESCs. Here we studied the methylation patterns of two differentially methylated regions (DMRs), SNRPN and H19/IGF2 DMRs, during the derivation of monkey ESCs. We show that the SNRPN DMR is characteristically methylated at maternal alleles, whereas the H19/IGF2 DMR is globally highly methylated, with unusual methylation on the maternal alleles. These methylation patterns remain stable from the early stages of ESC derivation to late passages of monkey ESCs and following differentiation. Importantly, the methylation status of H19/IGF2 DMR and the expression levels of IGF2, H19, and DNMT3B mRNAs in early embryo-derived cells were correlated with their capacity to generate genuine ESC lines. Thus, we propose that these markers could be useful to predict the outcomes of establishing an ESC line in primates.

Keywords: Embryonic stem cell; Epigenetic; H19/IGF2; Imprinted genes; Methylation; Non-human primate; SNRPN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA Methylation
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Epigenomics
  • Genomic Imprinting
  • Insulin-Like Growth Factor II / genetics*
  • Macaca mulatta
  • Mice
  • Mice, SCID
  • RNA, Long Noncoding / genetics*
  • Teratoma / pathology
  • Transplantation, Heterologous
  • snRNP Core Proteins / genetics*


  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • snRNP Core Proteins
  • Insulin-Like Growth Factor II