PubMed:18362916 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":206,"end":208},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":329,"end":331},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":500,"end":502},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":539,"end":541},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":558,"end":560},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":667,"end":669},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T12","span":{"begin":904,"end":906},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T13","span":{"begin":941,"end":943},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T15","span":{"begin":1158,"end":1160},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T16","span":{"begin":1281,"end":1283},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T18","span":{"begin":1404,"end":1406},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T20","span":{"begin":1423,"end":1425},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T21","span":{"begin":1504,"end":1506},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T22","span":{"begin":1522,"end":1524},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T24","span":{"begin":1535,"end":1537},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T26","span":{"begin":1736,"end":1738},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T28","span":{"begin":1960,"end":1962},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0012817"},{"id":"A2","pred":"mondo_id","subj":"T1","obj":"0017387"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0012817"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"0017387"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0012817"},{"id":"A6","pred":"mondo_id","subj":"T5","obj":"0017387"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0012817"},{"id":"A8","pred":"mondo_id","subj":"T7","obj":"0017387"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0006541"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"0012817"},{"id":"A11","pred":"mondo_id","subj":"T10","obj":"0017387"},{"id":"A12","pred":"mondo_id","subj":"T12","obj":"0006541"},{"id":"A13","pred":"mondo_id","subj":"T13","obj":"0012817"},{"id":"A14","pred":"mondo_id","subj":"T13","obj":"0017387"},{"id":"A15","pred":"mondo_id","subj":"T15","obj":"0006541"},{"id":"A16","pred":"mondo_id","subj":"T16","obj":"0012817"},{"id":"A17","pred":"mondo_id","subj":"T16","obj":"0017387"},{"id":"A18","pred":"mondo_id","subj":"T18","obj":"0012817"},{"id":"A19","pred":"mondo_id","subj":"T18","obj":"0017387"},{"id":"A20","pred":"mondo_id","subj":"T20","obj":"0006541"},{"id":"A21","pred":"mondo_id","subj":"T21","obj":"0006541"},{"id":"A22","pred":"mondo_id","subj":"T22","obj":"0012817"},{"id":"A23","pred":"mondo_id","subj":"T22","obj":"0017387"},{"id":"A24","pred":"mondo_id","subj":"T24","obj":"0012817"},{"id":"A25","pred":"mondo_id","subj":"T24","obj":"0017387"},{"id":"A26","pred":"mondo_id","subj":"T26","obj":"0012817"},{"id":"A27","pred":"mondo_id","subj":"T26","obj":"0017387"},{"id":"A28","pred":"mondo_id","subj":"T28","obj":"0012817"},{"id":"A29","pred":"mondo_id","subj":"T28","obj":"0017387"}],"text":"REST maintains self-renewal and pluripotency of embryonic stem cells.\nThe neuronal repressor REST (RE1-silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem (ES) cells, but its role in these cells is unclear. Here we show that REST maintains self-renewal and pluripotency in mouse ES cells through suppression of the microRNA miR-21. We found that, as with known self-renewal markers, the level of REST expression is much higher in self-renewing mouse ES cells than in differentiating mouse ES (embryoid body, EB) cells. Heterozygous deletion of Rest (Rest+/-) and its short-interfering-RNA-mediated knockdown in mouse ES cells cause a loss of self-renewal-even when these cells are grown under self-renewal conditions-and lead to the expression of markers specific for multiple lineages. Conversely, exogenously added REST maintains self-renewal in mouse EB cells. Furthermore, Rest+/- mouse ES cells cultured under self-renewal conditions express substantially reduced levels of several self-renewal regulators, including Oct4 (also called Pou5f1), Nanog, Sox2 and c-Myc, and exogenously added REST in mouse EB cells maintains the self-renewal phenotypes and expression of these self-renewal regulators. We also show that in mouse ES cells, REST is bound to the gene chromatin of a set of miRNAs that potentially target self-renewal genes. Whereas mouse ES cells and mouse EB cells containing exogenously added REST express lower levels of these miRNAs, EB cells, Rest+/- ES cells and ES cells treated with short interfering RNA targeting Rest express higher levels of these miRNAs. At least one of these REST-regulated miRNAs, miR-21, specifically suppresses the self-renewal of mouse ES cells, corresponding to the decreased expression of Oct4, Nanog, Sox2 and c-Myc. Thus, REST is a newly discovered element of the interconnected regulatory network that maintains the self-renewal and pluripotency of mouse ES cells."}