期刊
NATURE GENETICS
卷 42, 期 12, 页码 1113-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.710
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资金
- Howard Hughes Medical Institute Funding Source: Medline
- NHLBI NIH HHS [1 RC2-HL102815, RC2 HL102815, K08 HL089150] Funding Source: Medline
- NIH HHS [DP2 OD006670, DP2 OD006670-01, 1DP2OD00667-01] Funding Source: Medline
The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome(1-5), resulting in altered patterns of gene expression(2,6-9). 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.
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