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dc.contributor.authorShepherd, Maggie
dc.contributor.authorHattersley, Andrew
dc.date.accessioned2019-02-08T15:30:49Z
dc.date.available2019-02-08T15:30:49Z
dc.date.issued2019-01-08
dc.identifier.citationChia CY [et al]. GATA6 Cooperates with EOMES/SMAD2/3 to Deploy the Gene Regulatory Network Governing Human Definitive Endoderm and Pancreas Formation. Stem Cell Reports. 2019 Jan 8;12(1):57-70.en_US
dc.identifier.pmid30629940
dc.identifier.doi10.1016/j.stemcr.2018.12.003
dc.identifier.urihttps://rde.dspace-express.com/handle/123456789/620954
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_US
dc.language.isoenen_US
dc.publisherCell Pressen_US
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S2213-6711(18)30522-8en_US
dc.rightsThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en_US
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen_US
dc.titleGATA6 Cooperates with EOMES/SMAD2/3 to Deploy the Gene Regulatory Network Governing Human Definitive Endoderm and Pancreas Formationen_US
dc.typeJournal Articleen_US
dc.identifier.journalStem Cell Reportsen_US
dc.description.noteThis article is freely available via Open Access. Click on the link to the Publisher's site to access the full-text.en_US
dc.type.versionPublisheden_US
dc.description.admin-notePublished (Open Access)en_US


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