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Open Access Highly Accessed Research article

Stability of genomic imprinting in human induced pluripotent stem cells

Hitoshi Hiura1, Masashi Toyoda23, Hiroaki Okae1, Masahiro Sakurai1, Naoko Miyauchi1, Akiko Sato1, Nobutaka Kiyokawa2, Hajime Okita2, Yoshitaka Miyagawa2, Hidenori Akutsu2, Koichiro Nishino24, Akihiro Umezawa2* and Takahiro Arima1*

Author affiliations

1 Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai, 980-8575, Japan

2 Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Ohkura Setagaya-ku, Tokyo, 157-8535, Japan

3 Research team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, Japan

4 Laboratory of Veterinary Biochemistry and Molecular Biology, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen-Kibanadai-Nishi, Miyazaki, 889-2192, Japan

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Citation and License

BMC Genetics 2013, 14:32  doi:10.1186/1471-2156-14-32

Published: 30 April 2013

Abstract

Background

hiPSCs are generated through epigenetic reprogramming of somatic tissue. Genomic imprinting is an epigenetic phenomenon through which monoallelic gene expression is regulated in a parent-of-origin-specific manner. Reprogramming relies on the successful erasure of marks of differentiation while maintaining those required for genomic imprinting. Loss of imprinting (LOI), which occurs in many types of malignant tumors, would hinder the clinical application of hiPSCs.

Results

We examined the imprinting status, expression levels and DNA methylation status of eight imprinted genes in five independently generated hiPSCs. We found a low frequency of LOI in some lines. Where LOI was identified in an early passage cell line, we found that this was maintained through subsequent passages of the cells. Just as normal imprints are maintained in long-term culture, this work suggests that abnormal imprints are also stable in culture.

Conclusions

Analysis of genomic imprints in hiPSCs is a necessary safety step in regenerative medicine, with relevance both to the differentiation potential of these stem cells and also their potential tumorigenic properties.

Keywords:
Genomic imprinting; Loss of imprinting (LOI); DNA methylation; Histone modification; Human induced pluripotent cells