Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/85530
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dc.contributor.authorChia, Crystal Y.en
dc.contributor.authorMadrigal, Pedroen
dc.contributor.authorDenil, Simon L.I.J.en
dc.contributor.authorMartinez, Ikeren
dc.contributor.authorGarcia-Bernardo, Joseen
dc.contributor.authorEl-Khairi, Rannaen
dc.contributor.authorChhatriwala, Mariyaen
dc.contributor.authorShepherd, Maggie H.en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorVallier, Ludovicen
dc.contributor.authorDunn, Norris Rayen
dc.date.accessioned2019-07-10T02:02:24Zen
dc.date.accessioned2019-12-06T16:05:27Z-
dc.date.available2019-07-10T02:02:24Zen
dc.date.available2019-12-06T16:05:27Z-
dc.date.issued2019en
dc.identifier.citationChia, C. Y., Madrigal, P., Denil, S. L. I. J., Martinez, I., Garcia-Bernardo, J., El-Khairi, R., . . . Vallier, L. (2019). GATA6 cooperates with EOMES/SMAD2/3 to deploy the gene regulatory network governing human definitive endoderm and pancreas formation. Stem Cell Reports, 12(1), 57-70. doi:10.1016/j.stemcr.2018.12.003en
dc.identifier.urihttps://hdl.handle.net/10356/85530-
dc.description.abstractHeterozygous de novo mutations in GATA6 are the most frequent cause of pancreatic agenesis in humans. In mice, however, a similar phenotype requires the biallelic loss of Gata6 and its paralog Gata4. To elaborate the human-specific requirements for GATA6, we chose to model GATA6 loss in vitro by combining both gene-edited and patient-derived pluripotent stem cells (hPSCs) and directed differentiation toward β-like cells. We find that GATA6 heterozygous hPSCs show a modest reduction in definitive endoderm (DE) formation, while GATA6-null hPSCs fail to enter the DE lineage. Consistent with these results, genome-wide studies show that GATA6 binds and cooperates with EOMES/SMAD2/3 to regulate the expression of cardinal endoderm genes. The early deficit in DE is accompanied by a significant reduction in PDX1+ pancreatic progenitors and C-PEPTIDE+ β-like cells. Taken together, our data position GATA6 as a gatekeeper to early human, but not murine, pancreatic ontogeny.en
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en
dc.description.sponsorshipEDB (Economic Devt. Board, S’pore)en
dc.format.extent14 p.en
dc.language.isoenen
dc.relation.ispartofseriesStem Cell Reportsen
dc.rights© 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectScience::Medicineen
dc.subjectGATA6en
dc.subjectDefinitive Endodermen
dc.titleGATA6 cooperates with EOMES/SMAD2/3 to deploy the gene regulatory network governing human definitive endoderm and pancreas formationen
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en
dc.contributor.schoolSchool of Biological Sciencesen
dc.identifier.doi10.1016/j.stemcr.2018.12.003en
dc.description.versionPublished versionen
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