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

Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells Sabine Loewer1,2,3,4, Moran N. Cabili5,6, Mitchell Guttman5,7, Yuin-Han Loh1,2,3,4, Kelly Thomas5,8, In Hyun Park1,2,3,4,12, Manuel Garber5, Matthew Curran1,3, Tamer Onder1,2,3,4, Suneet Agarwal1,2,3, Philip D. Manos1,3,4, Sumon Datta1,3,4, Eric S. Lander5,6,7, Thorsten M. Schlaeger1,3,4, George Q. Daley1,2,3,4,8,9, and John L. Rinn5,10,11 1Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Children’s Hospital Boston and Dana Farber Cancer Institute, Boston MA, USA 2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA, USA 3Harvard Stem Cell Institute, Cambridge MA, USA 4Stem Cell Program, Children’s Hospital Boston, Boston MA, USA 5The Broad Institute of Harvard and MIT, Cambridge MA, USA 6Department of Systems Biology, Harvard Medical School, Boston MA, USA 7Department of Biology, Massachusetts Institute of Technology, Cambridge MA, USA 8Division of Hematology, Brigham and Women’s Hospital, Boston MA, USA 9Howard Hughes Medical Institute, Chevy Chase MD, USA 10Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge MA, USA 11Department of Pathology, Beth Israel and Deaconess Medical Center, Harvard Medical School, Boston MA, USA Abstract The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome1-5, resulting in altered patterns of gene expression2,6-9. 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 10 lincRNAs whose expression was elevated in iPSCs compared with embryonic stem cells (ESCs), suggesting that their activation may promote