Format

Send to

Choose Destination
Int J Stem Cells. 2019 Mar 30;12(1):31-42. doi: 10.15283/ijsc18084.

Alteration of Genomic Imprinting Status of Human Parthenogenetic Induced Pluripotent Stem Cells during Neural Lineage Differentiation.

Lee HJ1,2, Choi NY1,2, Lee SW1,2, Lee Y1,2, Ko K3, Kim GJ4, Hwang HS5, Ko K1,2,6.

Author information

1
Departement of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea.
2
Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.
3
Departments of Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
4
Departments of Obstetrics and Gynecology, College of Medicine, Chung-Ang University, Seoul, Korea.
5
Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Korea.
6
Research Institute of Medical Science, Konkuk University, Seoul, Korea.

Abstract

Background and Objectives:

Genomic imprinting modulates growth and development in mammals and is associated with genetic disorders. Although uniparental embryonic stem cells have been used to study genomic imprinting, there is an ethical issue associated with the destruction of human embryos. In this study, to investigate the genomic imprinting status in human neurodevelopment, we used human uniparental induced pluripotent stem cells (iPSCs) that possessed only maternal alleles and differentiated into neural cell lineages.

Methods:

Human somatic iPSCs (hSiPSCs) and human parthenogenetic iPSCs (hPgiPSCs) were differentiated into neural stem cells (NSCs) and named hSi-NSCs and hPgi-NSCs respectively. DNA methylation and gene expression of imprinted genes related neurodevelopment was analyzed during reprogramming and neural lineage differentiation.

Results:

The DNA methylation and expression of imprinted genes were altered or maintained after differentiation into NSCs. The imprinting status in NSCs were maintained after terminal differentiation into neurons and astrocytes. In contrast, gene expression was differentially presented in a cell type-specific manner.

Conclusions:

This study suggests that genomic imprinting should be determined in each neural cell type because the genomic imprinting status can differ in a cell type-specific manner. In addition, the in vitro model established in this study would be useful for verifying the epigenetic alteration of imprinted genes which can be differentially changed during neurodevelopment in human and for screening novel imprinted genes related to neurodevelopment. Moreover, the confirmed genomic imprinting status could be used to find out an abnormal genomic imprinting status of imprinted genes related with neurogenetic disorders according to uniparental genotypes.

KEYWORDS:

Genomic imprinting; Induced-pluripotent stem cells; Neural stem cells; Parthenogenetic cells; in vitro model

Supplemental Content

Full text links

Icon for Inforang Icon for PubMed Central
Loading ...
Support Center