Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.
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.
Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, Massachusetts, USA.
Sabine
S
Loewer
Moran N
MN
Cabili
Mitchell
M
Guttman
Yuin-Han
YH
Loh
Kelly
K
Thomas
In Hyun
IH
Park
Manuel
M
Garber
Matthew
M
Curran
Tamer
T
Onder
Suneet
S
Agarwal
Philip D
PD
Manos
Sumon
S
Datta
Eric S
ES
Lander
Thorsten M
TM
Schlaeger
George Q
GQ
Daley
John L
JL
Rinn
D065150:Cellular Reprogramming / Q000235:genetics*; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D022661:RNA, Untranslated; D014157:Transcription Factors