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

Na Young Choi; Jin Seok Bang; Hye Jeong Lee; Yo Seph Park; Minseong Lee; Dahee Jeong; Kisung Ko; Dong Wook Han; Hyung-Min Chung; Gwang Jun Kim; Seung-Hyuk Shim; Han Sung Hwang; Kinarm Ko

doi:10.1080/15592294.2018.1460033

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

Epigenetics. 2018;13(4):343-351. doi: 10.1080/15592294.2018.1460033. Epub 2018 May 3.

Authors

Na Young Choi^{1

2}, Jin Seok Bang^{1

2}, Hye Jeong Lee^{1

2}, Yo Seph Park^{1

2}, Minseong Lee^{1

2}, Dahee Jeong^{1

2}, Kisung Ko³, Dong Wook Han^{1

4}, Hyung-Min Chung¹, Gwang Jun Kim⁵, Seung-Hyuk Shim⁶, Han Sung Hwang⁶, Kinarm Ko^{1

2

4

7}

Affiliations

¹ a Department of Stem Cell Biology, School of Medicine , Konkuk University , Seoul 05029 , Korea.
² b Center for Stem Cell Research , Institute of Advanced Biomedical Science, Konkuk University , Seoul 05029 , Korea.
³ c Department of Medicine, College of Medicine , Chung-Ang University , Seoul 06974 , Korea.
⁴ d KU Open-Innovation Center , Institute of Biomedical Science and Technology, Konkuk University , Seoul 05029 , Korea.
⁵ e Department of Pediatrics, College of Medicine , Chung-Ang University , Seoul 06973 , Korea.
⁶ f Department of Obstetrics and Gynecology , School of Medicine, Konkuk University , Seoul 05030 , Korea.
⁷ g Research Institute of Medical Science , Konkuk University , Seoul 05029 , Korea.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cells, Cultured
CpG Islands
DNA Methylation*
Female
Gene Expression Profiling / methods
Gene Expression Regulation
Genomic Imprinting*
Humans
Induced Pluripotent Stem Cells / cytology*
Oligonucleotide Array Sequence Analysis / methods
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / pathology
Parthenogenesis
Sequence Analysis, DNA
Teratoma / genetics*
Teratoma / pathology

Supplementary concepts

Teratoma, Ovarian

Grants and 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).