{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:01:01Z","timestamp":1785409261968,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,7]]},"group-title":"Developmental Biology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["Z01-ES-101585"],"award-info":[{"award-number":["Z01-ES-101585"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  GLIS3 plays a critical role in pancreatic \u03b2 cells and diabetes, being one of only a few genes implicated in Type 1, Type 2, and Gestational diabetes. In addition to \u03b2 cells, GLIS3 is expressed embryonically in bipotent and proendocrine progenitor cells, suggesting a role in endocrine lineage development in mice. We hypothesize that GLIS3 is playing important roles in endocrine development as well as during \u03b2 cell differentiation. We utilized single cell RNA-sequencing at three different timepoints (embryonic day (e)13.5, e15.5, and e18.5) and single nucleus (sn)ATAC-sequencing at e15.5 in both wild type (WT) and\n                  <jats:italic>Glis3<\/jats:italic>\n                  Knockout (\n                  <jats:italic>Glis3<\/jats:italic>\n                  KO) mouse embryos. This analysis revealed that the numbers of bipotent, proendocrine progenitor, and all subsequent endocrine cells were proportionately reduced in\n                  <jats:italic>Glis3<\/jats:italic>\n                  KO mice. Additionally, loss of GLIS3 function generates a unique subpopulation of cells that fail to upregulate\n                  <jats:italic>Ins2<\/jats:italic>\n                  transcription and downregulate expression of several ribosomal and oxidative phosphorylation genes normally repressed during pre\u03b2 to \u03b2 cell differentiation. Our study therefore shows that GLIS3 regulates two distinct stages: the embryonic generation\/differentiation of bipotent cells and the differentiation of pre\u03b2 to \u03b2 cells. Dysregulation of these two stages provides a causal mechanism for the development of neonatal diabetes in GLIS3-deficiency.\n                <\/jats:p>","DOI":"10.64898\/2026.01.06.697979","type":"posted-content","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:55:11Z","timestamp":1767830111000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification of distinct functions of GLIS3 in \u03b2-cell generation critical to prevention of neonatal diabetes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-6502","authenticated-orcid":false,"given":"David W.","family":"Scoville","sequence":"first","affiliation":[{"name":"Cell Biology Group, Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3050-1909","authenticated-orcid":false,"given":"Sara A.","family":"Grimm","sequence":"additional","affiliation":[{"name":"Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[{"name":"Genomics Core Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5576-5647","authenticated-orcid":false,"given":"Benedict","family":"Anchang","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National 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