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Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells
2015-01-13
Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells "C:\Users\kurtw_000\Box Sync\DocDR\2014\01-31-2014d1002\Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells.pdf" Abstract Telomere shortening is associated with organismal aging. iPS cells have been recently derived from old patients; however, it is not known whether telomere chromatin acquires the same characteristics as in ES cells. We show here that telomeres are elongated in iPS cells compared to the parental differentiated cells both when using four (Oct3/4, Sox2, Klf4, cMyc) or three (Oct3/4, Sox2, Klf4) reprogramming factors and both from young and aged individuals. We demonstrate genetically that, during reprogram- ming, telomere elongation is usually mediated by telomerase and that iPS telomeres acquire the epige- netic marks of ES cells, including a low density of tri- methylated histones H3K9 and H4K20 and increased abundance of telomere transcripts. Finally, reprog- ramming ef?ciency of cells derived from increasing generations of telomerase-de?cient mice shows a dramatic decrease in iPS cell ef?ciency, a defect that is restored by telomerase reintroduction. Together, these results highlight the importance of telomere biology for iPS cell generation and function- ality. some notes q -We show here that telomeres are elongated in iPS cells compared to the parental differentiated cells both when using four (Oct3/4, Sox2, Klf4, cMyc) or three (Oct3/4, Sox2, Klf4) reprogramming factors and both from young and aged individuals. ^wow quite surprising and important -cMyc Is Dispensable for Telomerase Activation in Mouse iPS Cells -Telomere Elongation by Telomerase in iPS Cells -Impaired iPS Cell Generation from Late-Generation Terc / MEF with Critically Short Telomeres -Telomeric Heterochromatin in iPS Cells Acquires ES Cell Features -Increased Telomere Transcription in iPS Cells -Telomere Elongation in iPS Cells Derived from Old Donors -Generation of mouse iPS cells -TRF analysis -MEF: mouse embryonic fibroblast -Q-FISH analysis -B1-SINE Cobra Analysis for Global DNA Methylation -Analysis of Genomic Subtelomeric DNA Methylation -ChIP Assay
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