Telomereelongationininducedpluripotentstemcells from dyskeratosis congenita patients

. We investigated whether defects in telo-merasefunctionwouldlimitderivationandmaintenanceofiPScellsfrom patients with DC. Here we show that reprogrammed DC cellsovercomeacriticallimitationintelomeraseRNAcomponent( TERC)levels to restore telomere maintenance and self-renewal. We dis-coveredthat TERC upregulationisafeatureofthepluripotentstate,that several telomerase components are targeted by pluripotency-associated transcription factors, and that in autosomal dominantDC, transcriptional silencing accompanies a 39 deletion at theTERC locus. Our results demonstrate that reprogramming restorestelomere elongation in DC cells despite genetic lesions affectingtelomerase, and show that strategies to increase TERC expressionmay be therapeutically beneficial in DC patients.Reprogramming of somatic cells to a state of pluripotency is char-acterized by prolonged self-renewal, implying induction of telomeremaintenance mechanisms. Recently, it was reported that reprogram-mingofmousecellswasaccompaniedbyelongationoftelomeres