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 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.
Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Jonathan H
JH
Teichroeb
Dean H
DH
Betts
Homayoun
H
Vaziri
D002460:Cell Line; D041321:Chromosomes, Human, X / Q000235:genetics*; D016000:Cluster Analysis; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D050172:Genes, X-Linked / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D013489:Suppression, Genetic; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics*
D008565:Membrane Proteins; C490237:NNAT protein, human; D009419:Nerve Tissue Proteins