Suppression of the imprinted gene NNAT and X-chromosome gene activation in isogenic human iPS cells

Genetic comparison between human embryonic stem cells and induced pluripotent stem cells has been hampered by genetic variation. To solve this problem, we have developed an isogenic system that allows direct comparison of induced pluripotent stem cells (hiPSCs) to their genetically matched human emb...

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Bibliographic Details
Published in:PloS one 2011-10, Vol.6 (10), p.e23436
Main Authors: Teichroeb, Jonathan H, Betts, Dean H, Vaziri, Homayoun
Format: Article
Language:English
Subjects:
Biology
Biophysics
Book publishing
Cell Line
Chromosomes, Human, X - genetics
Cloning
Cluster Analysis
Comparative analysis
Dentistry
DNA Methylation - genetics
Embryo cells
Embryonic stem cells
Embryos
Epigenetics
Female
Fibroblasts
Gene expression
Gene Expression Profiling
Gene regulation
Genes
Genes, X-Linked - genetics
Genetic aspects
Genetic diversity
Genetic Loci - genetics
Genome, Human - genetics
Genomes
Genomic imprinting
Genomic Imprinting - genetics
Humans
Imprinting
Induced Pluripotent Stem Cells - metabolism
Membrane Proteins - genetics
Nerve Tissue Proteins - genetics
Oligonucleotide Array Sequence Analysis
Physiology
Pluripotency
Polymerase Chain Reaction
Stem cells
Suppression, Genetic
Transcription
Transcription (Genetics)
Transcription, Genetic
Transcriptional Activation - genetics
X Chromosomes
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Summary:Genetic comparison between human embryonic stem cells and induced pluripotent stem cells has been hampered by genetic variation. To solve this problem, we have developed an isogenic system that allows direct comparison of induced pluripotent stem cells (hiPSCs) to their genetically matched human embryonic stem cells (hESCs). We show that hiPSCs have a highly similar transcriptome to hESCs. Global transcriptional profiling identified 102-154 genes (>2 fold) that showed a difference between isogenic hiPSCs and hESCs. A stringent analysis identified NNAT as a key imprinted gene that was dysregulated in hiPSCs. Furthermore, a disproportionate number of X-chromosome localized genes were over-expressed in female hiPSCs. Our results indicate that despite a remarkably close transcriptome to hESCs, isogenic hiPSCs have alterations in imprinting and regulation of X-chromosome genes.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0023436