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

Nat Genet. 2010 Dec;42(12):1113-7. doi: 10.1038/ng.710. Epub 2010 Nov 7.

Abstract

The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome, resulting in altered patterns of gene expression. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cellular Reprogramming / genetics*
  • Cluster Analysis
  • Embryonic Stem Cells / metabolism
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Genetic Loci / genetics
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Open Reading Frames / genetics
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • RNA, Untranslated
  • Transcription Factors

Associated data

  • GEO/GSE24182