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Heterozygous 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.
Pubmed ID: 30629940
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Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.
View all literature mentionsA nonprofit organization offering research and clinical grade pluripotent stem cell lines, cytogenetic testing, quality control testing and cell banking services to researchers worldwide. The organization is focused on enhancing and expanding the study of human pluripotent stem cells by supporting basic research; establishing research protocols; creating and distributing cell lines; providing training to scientists worldwide; and supporting efforts to unlock the therapeutic potential of stem cell technologies. As home to the Wisconsin International Stem Cell (WISC) Bank, and previously the first US National Stem Cell Bank, WiCell serves the worldwide scientific stem cell community through banking, characterization, and distribution of stem cell lines as well as providing technical support. WiCell also offers cytogenetic services, quality control testing services and clinical grade cell lines to researchers across the globe.
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