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Hindi GATA6 and its Roles in Human Pancreas Development
Abstract
Understanding the regulation of pancreatic development is fundamental for the identification of novel therapeutic options for the highly prevalent diabetic patients all over the world. GATA6 mutations are associated with a broad pancreatic phenotype spectrum from severe pancreas agenesis and neonatal diabetes to the adult onset of diabetes. Many studies in mice verified the critical roles of GATA6 in pancreas development, however, phenotypes disparity is very large between human and mice. To understand the underlying mechanism of the human phenotypes, using human Pluripotent Stem Cells (hPSCs) to model the GATA6 deficiency in vitro becomes to be a very efficient research strategy. Deficient GATA6 gene dosage disrupts the differentiation of human pancreatic progenitors, leads to impaired formation of pancreatic β-like cells and the pancreas. Except for the gene dosage, GATA6 was identified activating transcription in its nearby genes temporally, which further activates cardiomyocyte and endoderm gene network through chromatin binding in intergenic regions without a GATA-binding motif. The elucidation of the GATA6 function in the pancreas can indicate a novel therapy strategy i.e. stem cell therapy.
