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Pdx1 expression in human-derived stem cells is used as a marker for induced pancreatic precursor cells. Unfortunately, the differentiation efficiency of human pancreatic progenitors into functional \u03b2-cells is poor. In order to gain insight into the genes that Pdx1 regulates during differentiation, we performed Pdx1 chromatin immunoprecipitation followed by high-throughput sequencing of embryonic day (e) 13.5 and 15.5 mouse pancreata. From this, we identified the transcription factor Teashirt zinc finger 1 (Tshz1) as a direct Pdx1 target. Tshz1 is expressed in developing and adult insulin- and glucagon-positive cells. Endocrine cells are properly specified in Tshz1-null embryos, but critical regulators of \u03b2-cell (Pdx1 and Nkx6.1) and \u03b1-cell (MafB and Arx) formation and function are downregulated. Adult Tshz1+\/\u2212 mice display glucose intolerance due to defects in glucose-stimulated insulin secretion associated with reduced Pdx1 and Clec16a expression in Tshz1+\/\u2212 islets. Lastly, we demonstrate that TSHZ1 levels are reduced in human islets of donors with type 2 diabetes. Thus, we position Tshz1 in the transcriptional network of maturing \u03b2-cells and suggest that its dysregulation could contribute to the islet phenotype of human type 2 diabetes.<\/jats:p>","DOI":"10.2337\/db14-1443","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T02:32:16Z","timestamp":1430188336000},"page":"2905-2914","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":20,"title":["Tshz1 Regulates Pancreatic \u03b2-Cell Maturation"],"prefix":"10.2337","volume":"64","author":[{"given":"Jeffrey C.","family":"Raum","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Soleimanpour","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Groff","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Cor\u00e9","sequence":"additional","affiliation":[{"name":"Institut de Biologie du D\u00e9veloppement de Marseille, UMR 7288, Aix-Marseille Universit\u00e9, CNRS, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Fasano","sequence":"additional","affiliation":[{"name":"Institut de Biologie du D\u00e9veloppement de Marseille, UMR 7288, Aix-Marseille Universit\u00e9, CNRS, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair N.","family":"Garratt","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology and Neurobiology, Center for Anatomy, Charit\u00e9 University Hospital Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Dai","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin C.","family":"Powers","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology & Metabolism, Department 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