{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:00:55Z","timestamp":1792242055547,"version":"4.4.0"},"reference-count":48,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":370,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["UC4 DK112217"],"award-info":[{"award-number":["UC4 DK112217"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["UC4 DK112232"],"award-info":[{"award-number":["UC4 DK112232"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["UC4 DK108132"],"award-info":[{"award-number":["UC4 DK108132"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["UC4 DK104119"],"award-info":[{"award-number":["UC4 DK104119"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Pennsylvania Diabetes Research Center","award":["P30 DK19525"],"award-info":[{"award-number":["P30 DK19525"]}]},{"name":"Vanderbilt Diabetes Research and Training Center","award":["P30 DK20593"],"award-info":[{"award-number":["P30 DK20593"]}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000901","name":"JDRF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Metabolism"],"published-print":{"date-parts":[[2019,3]]},"DOI":"10.1016\/j.cmet.2019.01.003","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T22:42:51Z","timestamp":1548974571000},"page":"769-783.e4","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":235,"title":["Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes"],"prefix":"10.1016","volume":"29","author":[{"given":"Yue J.","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Traum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Schug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin C.","family":"Powers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Feldman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Naji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyong-Mi","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus H.","family":"Kaestner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cmet.2019.01.003_bib1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.cmet.2018.07.002","article-title":"GABA and artesunate do not induce pancreatic alpha- to beta-cell transdifferentiation in\u00a0vivo","volume":"28","author":"Ackermann","year":"2018","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2019.01.003_bib2","first-page":"S62","article-title":"Diagnosis and classification of diabetes mellitus","volume":"33","year":"2009","journal-title":"Diabetes Care"},{"key":"10.1016\/j.cmet.2019.01.003_bib3","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nm.3488","article-title":"Multiplexed ion beam imaging of human breast tumors","volume":"20","author":"Angelo","year":"2014","journal-title":"Nat. Med."},{"key":"10.1016\/j.cmet.2019.01.003_bib4","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1369\/0022155415576541","article-title":"Characterization of antibodies to products of proinsulin processing using immunofluorescence staining of pancreas in multiple species","volume":"63","author":"Asadi","year":"2015","journal-title":"J.\u00a0Histochem. Cytochem."},{"key":"10.1016\/j.cmet.2019.01.003_bib50","doi-asserted-by":"crossref","first-page":"a007641","DOI":"10.1101\/cshperspect.a007641","article-title":"The pathogenesis and natural history of type 1 diabetes","volume":"2","author":"Atkinson","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.cmet.2019.01.003_bib5","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1007\/s00125-013-3159-7","article-title":"Pancreatic biopsies in type 1 diabetes: revisiting the myth of Pandora\u2019s box","volume":"57","author":"Atkinson","year":"2014","journal-title":"Diabetologia"},{"key":"10.1016\/j.cmet.2019.01.003_bib6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0140-6736(01)05415-0","article-title":"Type 1 diabetes: new perspectives on disease pathogenesis and treatment","volume":"358","author":"Atkinson","year":"2001","journal-title":"Lancet"},{"key":"10.1016\/j.cmet.2019.01.003_bib7","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","article-title":"Type 1 diabetes","volume":"383","author":"Atkinson","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.cmet.2019.01.003_bib8","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/s11892-014-0552-7","article-title":"Extracellular matrix components in the pathogenesis of type 1 diabetes","volume":"14","author":"Bogdani","year":"2014","journal-title":"Curr. Diab. Rep."},{"key":"10.1016\/j.cmet.2019.01.003_bib9","doi-asserted-by":"crossref","first-page":"883","DOI":"10.2337\/diab.31.10.883","article-title":"New perspectives on the microvasculature of the islets of Langerhans in the rat","volume":"31","author":"Bonner-Weir","year":"1982","journal-title":"Diabetes"},{"key":"10.1016\/j.cmet.2019.01.003_bib10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1056\/NEJM198508083130604","article-title":"In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis","volume":"313","author":"Bottazzo","year":"1985","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.cmet.2019.01.003_bib11","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1172\/JCI66514","article-title":"Epigenomic plasticity enables human pancreatic \u03b1 to \u03b2 cell reprogramming","volume":"123","author":"Bramswig","year":"2013","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.cmet.2019.01.003_bib12","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1016\/j.celrep.2018.02.032","article-title":"\u03b1 cell function and gene expression are compromised in type 1 diabetes","volume":"22","author":"Brissova","year":"2018","journal-title":"Cell Rep."},{"key":"10.1016\/j.cmet.2019.01.003_bib14","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/dmrr.2316","article-title":"Network for Pancreatic Organ Donors with Diabetes (nPOD): developing a tissue biobank for type 1 diabetes","volume":"28","author":"Campbell-Thompson","year":"2012","journal-title":"Diabetes Metab. Res. Rev."},{"key":"10.1016\/j.cmet.2019.01.003_bib15","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1007\/s00125-013-3043-5","article-title":"The diagnosis of insulitis in human type 1 diabetes","volume":"56","author":"Campbell-Thompson","year":"2013","journal-title":"Diabetologia"},{"key":"10.1016\/j.cmet.2019.01.003_bib16","doi-asserted-by":"crossref","first-page":"R100","DOI":"10.1186\/gb-2006-7-10-r100","article-title":"CellProfiler: image analysis software for identifying and quantifying cell phenotypes","volume":"7","author":"Carpenter","year":"2006","journal-title":"Genome Biol."},{"key":"10.1016\/j.cmet.2019.01.003_bib17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/cyto.a.23053","article-title":"Imaging mass cytometry","volume":"91","author":"Chang","year":"2017","journal-title":"Cytometry A"},{"key":"10.1016\/j.cmet.2019.01.003_bib18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1084\/jem.20111187","article-title":"Demonstration of islet-autoreactive CD8 T\u00a0cells in insulitic lesions from recent onset and long-term type 1 diabetes patients","volume":"209","author":"Coppieters","year":"2012","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.cmet.2019.01.003_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmet.2018.11.014","article-title":"A map of human type 1 diabetes progression by imaging mass cytometry","volume":"29","author":"Damond","year":"2019","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2019.01.003_bib20","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1056\/NEJM198605223142106","article-title":"Type I diabetes mellitus. A chronic autoimmune disease","volume":"314","author":"Eisenbarth","year":"1986","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.cmet.2019.01.003_bib21","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/1471-2105-11-367","article-title":"A flexible R package for nonnegative matrix factorization","volume":"11","author":"Gaujoux","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.cmet.2019.01.003_bib22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1126\/science.182.4108.171","article-title":"Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect","volume":"182","author":"Gerich","year":"1973","journal-title":"Science"},{"key":"10.1016\/j.cmet.2019.01.003_bib23","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.2869","article-title":"Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry","volume":"11","author":"Giesen","year":"2014","journal-title":"Nat. Methods"},{"key":"10.1016\/j.cmet.2019.01.003_bib24","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.cell.2018.07.010","article-title":"Deep profiling of mouse splenic architecture with Codex multiplexed imaging","volume":"174","author":"Goltsev","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.cmet.2019.01.003_bib25","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1242\/dev.129.10.2447","article-title":"Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors","volume":"129","author":"Gu","year":"2002","journal-title":"Development"},{"key":"10.1016\/j.cmet.2019.01.003_bib26","doi-asserted-by":"crossref","DOI":"10.1126\/science.aar7042","article-title":"Multiplexed protein maps link subcellular organization to cellular states","volume":"361","author":"Gut","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.cmet.2019.01.003_bib27","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1172\/JCI116835","article-title":"Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients","volume":"92","author":"Itoh","year":"1993","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.cmet.2019.01.003_bib28","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2337\/db12-0432","article-title":"The peri-islet basement membrane, a barrier to infiltrating leukocytes in type 1 diabetes in mouse and human","volume":"62","author":"Korpos","year":"2013","journal-title":"Diabetes"},{"key":"10.1016\/j.cmet.2019.01.003_bib29","article-title":"lmerTest package: tests in linear mixed effects models","volume":"82","author":"Kuznetsova","year":"2017","journal-title":"J.\u00a0Stat. Soft."},{"key":"10.1016\/j.cmet.2019.01.003_bib30","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/0016-5085(80)90371-6","article-title":"Blood\u00a0flow to the rabbit pancreas with special reference to the islets of Langerhans","volume":"79","author":"Lifson","year":"1980","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cmet.2019.01.003_bib31","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/BF01236270","article-title":"Identification of a lobe in the adult human pancreas rich in pancreatic polypeptide","volume":"17","author":"Malaisse-Lagae","year":"1979","journal-title":"Diabetologia"},{"key":"10.1016\/j.cmet.2019.01.003_bib32","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.cmet.2017.03.017","article-title":"Virgin beta cells persist throughout life at a neogenic niche within pancreatic islets","volume":"25","author":"van der Meulen","year":"2017","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2019.01.003_bib33","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2214\/ajr.151.3.493","article-title":"Severe acute\u00a0pancreatitis after percutaneous biopsy of the pancreas","volume":"151","author":"Mueller","year":"1988","journal-title":"AJR Am. J. Roentgenol."},{"key":"10.1016\/j.cmet.2019.01.003_bib34","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1900\/RDS.2009.6.97","article-title":"Type 1 diabetes development requires both CD4 and CD8 T\u00a0cells and can be reversed by non-depleting antibodies targeting both T\u00a0cell populations","volume":"6","author":"Phillips","year":"2009","journal-title":"Rev. Diabet. Stud."},{"key":"10.1016\/j.cmet.2019.01.003_bib35","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.2337\/diabetes.54.suppl_2.S52","article-title":"Autoantibodies in diabetes","volume":"54","author":"Pihoker","year":"2005","journal-title":"Diabetes"},{"key":"10.1016\/j.cmet.2019.01.003_bib36","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s12020-015-0534-9","article-title":"Beta-cell destruction and preservation in childhood and adult onset type 1 diabetes","volume":"49","author":"Poudel","year":"2015","journal-title":"Endocrine"},{"key":"10.1016\/j.cmet.2019.01.003_bib37","doi-asserted-by":"crossref","first-page":"e1003274","DOI":"10.1371\/journal.pgen.1003274","article-title":"Nkx6.1 Controls a gene regulatory network required for establishing and maintaining pancreatic Beta cell identity","volume":"9","author":"Schaffer","year":"2013","journal-title":"PLoS Genet."},{"key":"10.1016\/j.cmet.2019.01.003_bib38","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/nmeth.4391","article-title":"histoCAT: analysis of cell phenotypes and interactions in multiplex image cytometry data","volume":"14","author":"Schapiro","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.cmet.2019.01.003_bib39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.32614\/RJ-2016-021","article-title":"Mclust 5: clustering, classification and density estimation using gaussian finite mixture models","volume":"8","author":"Scrucca","year":"2016","journal-title":"R J"},{"key":"10.1016\/j.cmet.2019.01.003_bib40","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.2337\/db14-1752","article-title":"Loss of \u03b2-cell identity occurs in type 2 diabetes and is associated with islet amyloid deposits","volume":"64","author":"Spijker","year":"2015","journal-title":"Diabetes"},{"key":"10.1016\/j.cmet.2019.01.003_bib41","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/BF01271177","article-title":"The pancreatic polypeptide-rich lobe of the human pancreas: definitive identification of its derivation from the ventral pancreatic primordium","volume":"23","author":"Stefan","year":"1982","journal-title":"Diabetologia"},{"key":"10.1016\/j.cmet.2019.01.003_bib42","series-title":"R: A Language and Environment for Statistical Computing","author":"Team","year":"2013"},{"key":"10.1016\/j.cmet.2019.01.003_bib43","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/nature08894","article-title":"Conversion of adult pancreatic \u03b1-cells to \u03b2-cells after extreme \u03b2-cell loss","volume":"464","author":"Thorel","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.cmet.2019.01.003_bib45","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.08261","article-title":"First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic \u03b2-cell mass","volume":"4","author":"Wang","year":"2015","journal-title":"Elife"},{"key":"10.1016\/j.cmet.2019.01.003_bib46","doi-asserted-by":"crossref","first-page":"e67454","DOI":"10.1371\/journal.pone.0067454","article-title":"Regional differences in islet distribution in the human pancreas\u2013preferential beta-cell loss in the head region in patients with type 2 diabetes","volume":"8","author":"Wang","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.cmet.2019.01.003_bib47","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.cmet.2016.09.007","article-title":"Single-cell mass cytometry analysis of the human endocrine pancreas","volume":"24","author":"Wang","year":"2016","journal-title":"Cell Metab."},{"key":"10.1016\/j.cmet.2019.01.003_bib48","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1365-2249.2008.03860.x","article-title":"Analysis of islet inflammation in human type 1 diabetes","volume":"155","author":"Willcox","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"10.1016\/j.cmet.2019.01.003_bib49","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.cmet.2016.08.018","article-title":"RNA sequencing of single human islet cells reveals type 2 diabetes genes","volume":"24","author":"Xin","year":"2016","journal-title":"Cell Metab."}],"container-title":["Cell Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1550413119300038?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1550413119300038?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T07:31:53Z","timestamp":1761550313000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1550413119300038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":48,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["S1550413119300038"],"URL":"https:\/\/doi.org\/10.1016\/j.cmet.2019.01.003","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734995963.793569193","asserted-by":"object"}]},"ISSN":["1550-4131"],"issn-type":[{"value":"1550-4131","type":"print"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes","name":"articletitle","label":"Article Title"},{"value":"Cell Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cmet.2019.01.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"https:\/\/doi.org\/10.1016\/j.cmet.2018.11.014","name":"associatedlink","label":"CrossRef DOI link to the associated document"},{"value":"https:\/\/doi.org\/10.1016\/j.cmet.2018.11.016","name":"associatedlink","label":"CrossRef DOI link to the associated document"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Inc.","name":"copyright","label":"Copyright"}]}}