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

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

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

Abstract

BACKGROUND AND OBJECTIVE
S: 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.

Keyword

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

MeSH Terms

Alleles
Astrocytes
Cell Lineage
DNA Methylation
Embryonic Stem Cells
Embryonic Structures
Epigenomics
Ethics
Gene Expression
Genomic Imprinting*
Genotype
Growth and Development
Humans*
In Vitro Techniques
Induced Pluripotent Stem Cells*
Mammals
Mass Screening
Neural Stem Cells
Neurons
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