Generation of Mouse Parthenogenetic Epiblast Stem Cells and Their Imprinting Patterns

Int J Mol Sci. 2019 Oct 31;20(21):5428. doi: 10.3390/ijms20215428.

Abstract

Pluripotent stem cells can be established from parthenogenetic embryos, which only possess maternal alleles with maternal-specific imprinting patterns. Previously, we and others showed that parthenogenetic embryonic stem cells (pESCs) and parthenogenetic induced pluripotent stem cells (piPSCs) progressively lose the bimaternal imprinting patterns. As ESCs and iPSCs are naïve pluripotent stem cells, parthenogenetic primed pluripotent stem cells have not yet been established, and thus, their imprinting patterns have not been studied. Here, we first established parthenogenetic epiblast stem cells (pEpiSCs) from 7.5 dpc parthenogenetic implantation embryos and compared the expression patterns and DNA methylation status of the representative imprinted genes with biparental EpiSCs. We found that there were no striking differences between pEpiSCs and biparental EpiSCs with respect to morphology, pluripotency gene expression, and differentiation potential, but there were differences in the expression and DNA methylation status of imprinted genes (H19, Igf2, Peg1, and Peg3). Moreover, pEpiSCs displayed a different DNA methylation pattern compared with that of parthenogenetic neural stem cells (pNSCs), which showed a typical bimaternal imprinting pattern. These results suggest that both naïve pluripotent stem cells and primed pluripotent stem cells have an unstable imprinting status.

Keywords: embryonic stem cell (ESC); epiblast stem cell (EpiSC); imprinted gene; parthenogenesis.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cells, Cultured
  • DNA Methylation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genomic Imprinting / genetics*
  • Germ Layers / cytology
  • Germ Layers / metabolism*
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Insulin-Like Growth Factor II / genetics
  • Mice
  • Parthenogenesis / genetics*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • RNA, Long Noncoding / genetics

Substances

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