Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells

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Abstract
George Daley and John Rinn and colleagues identify large intergenic non-coding RNAs that are upregulated during reprogramming of induced pluripotent stem cells, and they show a functional role for large intergenic non-coding RNA-RoR in induced pluripotent stem cell derivation. The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome1,2,3,4,5, resulting in altered patterns of gene expression2,6,7,8,9. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs)10,11 that occurs upon derivation of human iPSCs and identify numerous lincRNAs whose expression is linked to pluripotency. Among these, we defined ten lincRNAs whose expression was elevated in iPSCs compared with embryonic stem cells, suggesting that their activation may promote the emergence of iPSCs. Supporting this, our results indicate that these lincRNAs are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such lincRNA (lincRNA-RoR) modulates reprogramming, thus providing a first demonstration for critical functions of lincRNAs in the derivation of pluripotent stem cells.