Related Experiment Video
Updated: Jul 10, 2026
12:13
Zinc-finger Nuclease Enhanced Gene Targeting in Human Embryonic Stem Cells
Published on: August 23, 2014
Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines.
Kee-Pyo Kim1, Alexandra Thurston, Christine Mummery
1Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), University of Nottingham, Centre for Biomolecular Sciences, Nottingham NG7 2RD, United Kingdom.
Genome Research
|November 9, 2007
Summary
Imprinted gene expression in human embryonic stem cells (hESCs) is vulnerable, with half showing variable allelic expression. Disrupted DNA methylation may cause this instability, necessitating imprinting analysis for hESC applications.
Area of Science:
- Genomics
- Epigenetics
- Stem Cell Biology
Background:
- Disregulation of imprinted genes is linked to cancer and affects stem cell differentiation.
- While mouse and primate stem cells show imprinting disruption, human cells were thought to be more stable.
- Understanding imprinting stability in human embryonic stem cells (hESCs) is crucial for safe stem cell therapies.
Purpose of the Study:
- To assess the allelic expression stability of imprinted genes in human embryonic stem cell lines.
- To identify imprinted genes vulnerable to expression changes in hESCs.
- To investigate potential mechanisms, like DNA methylation, underlying imprinting instability.
Main Methods:
- Analyzed allelic expression of 22 imprinted genes across 22 human embryonic stem cell lines.
- Identified heterozygous loci for expression analysis.
- Correlated expression variability with DNA methylation patterns in regulatory regions.
Main Results:
- Half of the examined imprinted genes (e.g., IPW, H19, MEG3, PEG10, IGF2) exhibited variable allelic expression between hESC lines.
- Seven genes (e.g., NDN, SNRPN, KCNQ1, CDKN1C) maintained consistent monoallelic expression.
- Four genes (TP73, IGF2R, WT1, SLC22A18) showed biallelic expression in hESCs, differing from their patterns in other tissues.
- MEST isoform 1, PEG10, and NESP55 variability correlated with DNA methylation changes.
Conclusions:
- Human embryonic stem cells display gene-specific imprinting instability.
- Disrupted DNA methylation is a potential mechanism driving imprinting variability in hESCs.
- Comprehensive imprinting analysis is essential for characterizing hESC lines for therapeutic use.
Related Concept Videos
02:30Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:14Maintenance of the ES Cell State
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
00:57Embryonic Stem Cells
Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...