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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,6,28]]},"abstract":"<jats:p>Delineating gene regulatory networks that orchestrate cell-type specification is a continuing challenge for developmental biologists. Single-cell analyses offer opportunities to address these challenges and accelerate discovery of rare cell lineage relationships and mechanisms underlying hierarchical lineage decisions. Here, we describe the molecular analysis of mouse pancreatic endocrine cell differentiation using single-cell transcriptomics, chromatin accessibility assays coupled to genetic labeling, and cytometry-based cell purification. We uncover transcription factor networks that delineate \u03b2-, \u03b1-, and \u03b4-cell lineages. Through genomic footprint analysis, we identify transcription factor\u2013regulatory DNA interactions governing pancreatic cell development at unprecedented resolution. Our analysis suggests that the transcription factor Neurog3 may act as a pioneer transcription factor to specify the pancreatic endocrine lineage. These findings could improve protocols to generate replacement endocrine cells from renewable sources, like stem cells, for diabetes therapy.<\/jats:p>","DOI":"10.1073\/pnas.2201267119","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:48Z","timestamp":1655942448000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Single-cell transcriptome and accessible chromatin dynamics during endocrine pancreas development"],"prefix":"10.1073","volume":"119","author":[{"given":"Eliza","family":"Duvall","sequence":"first","affiliation":[{"name":"Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecil M.","family":"Benitez","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-216X","authenticated-orcid":false,"given":"Krissie","family":"Tellez","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-8931","authenticated-orcid":false,"given":"Martin","family":"Enge","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip T.","family":"Pauerstein","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6788-8620","authenticated-orcid":false,"given":"Lingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-5167","authenticated-orcid":false,"given":"Songjoon","family":"Baek","sequence":"additional","affiliation":[{"name":"Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Quake","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2688-0988","authenticated-orcid":false,"given":"Jason P.","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan C.","family":"Sheffield","sequence":"additional","affiliation":[{"name":"Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5294-2521","authenticated-orcid":false,"given":"H. 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Duvall H. Arda S. Kim Data from \u201cSingle cell transcriptome analysis of endocrine pancreas development in mice.\u201d https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE146006. Accessed 8 June 2022."},{"key":"e_1_3_4_74_2","unstructured":"H. Arda S. Kim E. Duvall Data from \u201cOpen chromatin landscape of pancreatic endocrine progenitors.\u201d https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE65794. 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