Novel imprinted single CpG sites found by global DNA methylation analysis in human parthenogenetic induced pluripotent stem cells

ABSTRACT

Genomic imprinting is the process of epigenetic modification whereby genes are expressed in a parent-of-origin dependent manner; it plays an important role in normal growth and development. Parthenogenetic embryos contain only the maternal genome. Parthenogenetic embryonic stem cells could be useful for studying imprinted genes. In humans, mature cystic ovarian teratomas originate from parthenogenetic activation of oocytes; they are composed of highly differentiated mature tissues containing all three germ layers. To establish human parthenogenetic induced pluripotent stem cell lines (PgHiPSCs), we generated parthenogenetic fibroblasts from ovarian teratoma tissues. We compared global DNA methylation status of PgHiPSCs with that of biparental human induced pluripotent stem cells by using Illumina Infinium HumanMethylation450 BeadChip array. This analysis identified novel single imprinted CpG sites. We further tested DNA methylation patterns of two of these sites using bisulfite sequencing and described novel candidate imprinted CpG sites. These results confirm that PgHiPSCs are a powerful tool for identifying imprinted genes and investigating their roles in human development and diseases.

KEYWORDS:

• Parthenogenetic induced pluripotent stem cells
• parthenogenetic imprinting
• Illumina HumanMethylation450, 450K array
• genome-wide
• DNA methylation

Disclosure of potential conflicts of interest

The authors indicate no potential conflicts of interest.

Additional information

Funding

This research was supported by a fund [grant number 2016-ER6104-00] by Research of Korea Centers for Disease Control and Prevention and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [grant number 2018R1A2B6001072], and by the Technology Innovation Program [grant number 10063301] funded by Ministry of Trade, Industry & Energy (MI, Korea).