Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/145979
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dc.contributor.authorWang, Hao Feien_US
dc.contributor.authorWarrier, Tusharen_US
dc.contributor.authorFarran, Chadi A.en_US
dc.contributor.authorZheng, Zi Haoen_US
dc.contributor.authorXing, Qiao Ruien_US
dc.contributor.authorFullwood, Melissa Janeen_US
dc.contributor.authorZhang, Li-Fengen_US
dc.contributor.authorLi, Huen_US
dc.contributor.authorXu, Jianen_US
dc.contributor.authorLim, Tit-Mengen_US
dc.contributor.authorLoh, Yuin-Hanen_US
dc.date.accessioned2021-01-19T07:53:17Z-
dc.date.available2021-01-19T07:53:17Z-
dc.date.issued2020-
dc.identifier.citationWang, H. F., Warrier, T., Farran, C. A., Zheng, Z. H., Xing, Q. R., Fullwood, M. J., . . . Loh, Y.-H. (2020). Defining essential enhancers for pluripotent stem cells using a features-oriented CRISPR-Cas9 screen. Cell Reports, 33(4), 108309-. doi:10.1016/j.celrep.2020.108309en_US
dc.identifier.issn2211-1247en_US
dc.identifier.other0000-0001-8914-442X-
dc.identifier.other0000-0003-1123-0373-
dc.identifier.other0000-0003-0917-0017-
dc.identifier.other0000-0001-6194-6316-
dc.identifier.other0000-0002-4715-6454-
dc.identifier.urihttps://hdl.handle.net/10356/145979-
dc.description.abstractcis-regulatory elements (CREs) regulate the expression of genes in their genomic neighborhoods and influence cellular processes such as cell-fate maintenance and differentiation. To date, there remain major gaps in the functional characterization of CREs and the identification of their target genes in the cellular native environment. In this study, we perform a features-oriented CRISPR-utilized systematic (FOCUS) screen of OCT4-bound CREs using CRISPR-Cas9 to identify functional enhancers important for pluripotency maintenance in mESCs. From the initial 235 candidates tested, 16 CREs are identified to be essential stem cell enhancers. Using RNA-seq and genomic 4C-seq, we further uncover a complex network of candidate CREs and their downstream target genes, which supports the growth and self-renewal of mESCs. Notably, an essential enhancer, CRE111, and its target, Lrrc31, form the important switch to modulate the LIF-JAK1-STAT3 signaling pathway.en_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.description.sponsorshipNational Research Foundation (NRF)en_US
dc.language.isoenen_US
dc.relationNRF12018-02en_US
dc.relation1534n00153en_US
dc.relationNMRC/CBRG/0092/2015en_US
dc.relation.ispartofCell Reportsen_US
dc.rights© 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.subjectScience::Biological sciencesen_US
dc.titleDefining essential enhancers for pluripotent stem cells using a features-oriented CRISPR-Cas9 screenen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.organizationLaboratory for Epigenetics, Stem Cells and Cell Therapy, A*STARen_US
dc.identifier.doi10.1016/j.celrep.2020.108309-
dc.description.versionPublished versionen_US
dc.identifier.pmid33113365-
dc.identifier.scopus2-s2.0-85094618554-
dc.identifier.issue4en_US
dc.identifier.volume33en_US
dc.subject.keywordsCRISPR Screenen_US
dc.subject.keywordsOCT4-bounden_US
dc.description.acknowledgementWe thank Yu Tao, Fang Haitong, Nickolas Teo, Aloysi Aloysius Jun-Hui Quek, and Samantha Seah for technical assistance and editorial suggestions. Y.-H.L. is supported by the NRF Investigatorship Award ( NRF12018-02 ), a JCO Development Programme Grant ( 1534n00153 ), and the National Medical Research Council ( NMRC/CBRG/0092/2015 ).en_US
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