{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T06:06:03Z","timestamp":1792476363515,"version":"4.5.0"},"reference-count":37,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T00:00:00Z","timestamp":1474502400000},"content-version":"vor","delay-in-days":84,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30-DK19525"],"award-info":[{"award-number":["P30-DK19525"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020633","name":"BIRAX","doi-asserted-by":"crossref","award":["14BX14NHBG"],"award-info":[{"award-number":["14BX14NHBG"]}],"id":[{"id":"10.13039\/501100020633","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["UC4DK104119"],"award-info":[{"award-number":["UC4DK104119"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:p>Human pancreatic islets consist of multiple endocrine cell types. To facilitate the detection of rare cellular states and uncover population heterogeneity, we performed single-cell RNA sequencing (RNA-seq) on islets from multiple deceased organ donors, including children, healthy adults, and individuals with type 1 or type 2 diabetes. We developed a robust computational biology framework for cell type annotation. Using this framework, we show that \u03b1- and \u03b2-cells from children exhibit less well-defined gene signatures than those in adults. Remarkably, \u03b1- and \u03b2-cells from donors with type 2 diabetes have expression profiles with features seen in children, indicating a partial dedifferentiation process. We also examined a naturally proliferating \u03b1-cell from a healthy adult, for which pathway analysis indicated activation of the cell cycle and repression of checkpoint control pathways. Importantly, this replicating \u03b1-cell exhibited activated Sonic hedgehog signaling, a pathway not previously known to contribute to human \u03b1-cell proliferation. Our study highlights the power of single-cell RNA-seq and provides a stepping stone for future explorations of cellular heterogeneity in pancreatic endocrine cells.<\/jats:p>","DOI":"10.2337\/db16-0405","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T22:53:52Z","timestamp":1467327232000},"page":"3028-3038","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":415,"title":["Single-Cell Transcriptomics of the Human Endocrine Pancreas"],"prefix":"10.2337","volume":"65","author":[{"given":"Yue J.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Schug","sequence":"additional","affiliation":[{"name":"Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-Jae","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Naji","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 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