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

被引：807

作者：

Loewer, Sabine ^{[1
,2
,3
,4
,5
]}

Cabili, Moran N. ^{[6
,8
]}

Guttman, Mitchell ^{[6
,7
]}

Loh, Yuin-Han ^{[1
,2
,3
,4
,5
]}

Thomas, Kelly ^{[6
,9
]}

Park, In Hyun ^{[1
,2
,3
,4
,5
]}

Garber, Manuel ^{[6
]}

Curran, Matthew ^{[1
,2
,4
]}

Onder, Tamer ^{[1
,2
,3
,4
,5
]}

Agarwal, Suneet ^{[1
,2
,3
,4
]}

Manos, Philip D. ^{[1
,2
,4
,5
]}

Datta, Sumon ^{[1
,2
,4
,5
]}

Lander, Eric S. ^{[6
,7
,8
]}

Schlaeger, Thorsten M. ^{[1
,2
,4
,5
]}

Daley, George Q. ^{[1
,2
,3
,4
,5
,9
,10
]}

Rinn, John L. ^{[6
,11
,12
]}

机构：

[1] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA USA

[2] Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[4] Harvard Stem Cell Inst, Cambridge, MA USA

[5] Childrens Hosp Boston, Stem Cell Program, Boston, MA USA

[6] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA

[7] MIT, Dept Biol, Cambridge, MA USA

[8] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

[9] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA

[10] Howard Hughes Med Inst, Chevy Chase, MD USA

[11] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02115 USA

[12] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 12期

关键词：

DEVELOPMENTAL REGULATORS; EXPRESSION; GENERATION; POLYCOMB; TRANSCRIPTION; FIBROBLASTS; METHYLATION; COMPLEXES; NETWORK; TISSUE;

D O I：

10.1038/ng.710

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1113 / +

页数：6

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