{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:37:41Z","timestamp":1787683061977,"version":"build-2784847793"},"posted":{"date-parts":[[2025,3,19]]},"group-title":"Immunology","reference-count":95,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,19]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Type 1 diabetes (T1D) is a progressive autoimmune condition that culminates in the loss of insulin-producing beta cells. Pancreatic histopathology provides essential insights into disease initiation and progression yet an integrated perspective of\n                  <jats:italic>in situ<\/jats:italic>\n                  pathogenic processes is lacking due to limited sample availability, the dispersed nature of anatomical lesions, and often restricted analytical dimensionality. Here, we combined multiplexed immunostaining, high-magnification whole-slide imaging, digital pathology, and semi-automated image analysis strategies to interrogate pancreatic tail and head regions obtained from organ donors across T1D stages including at-risk and at-onset cases. Deconvolution of architectural features, endocrine cell composition, immune cell burden, and spatial relations of \u223c25,000 islets revealed a series of novel histopathological correlates especially in the prodromal disease stage preceding clinical T1D. Altogether, our comprehensive \u201csingle-islet\u201d analyses permit the reconstruction of a revised natural T1D history with implications for further histopathological investigations, considerations of pathogenetic modalities, and therapeutic interventions.\n                <\/jats:p>","DOI":"10.1101\/2025.03.18.644000","type":"posted-content","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T14:00:25Z","timestamp":1742392825000},"source":"Crossref","is-referenced-by-count":7,"title":["Integrated histopathology of the human pancreas throughout stages of type 1 diabetes progression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3602-4405","authenticated-orcid":false,"given":"Verena","family":"van der Heide","sequence":"first","affiliation":[{"name":"Marc and Jennifer Lipschultz Precision Immunology Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3795-3772","authenticated-orcid":false,"given":"Sara","family":"McArdle","sequence":"additional","affiliation":[{"name":"Microscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Cerosaletti","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute, Seattle, WA 98101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha","family":"Gnjatic","sequence":"additional","affiliation":[{"name":"Marc and Jennifer Lipschultz Precision Immunology Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY 10029, USA"},{"name":"Tisch Cancer Institute, Department of Medicine, ISMMS, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1918-9216","authenticated-orcid":false,"given":"Zbigniew","family":"Mikulski","sequence":"additional","affiliation":[{"name":"Microscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-0958","authenticated-orcid":false,"given":"Amanda L.","family":"Posgai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2614-0813","authenticated-orcid":false,"given":"Irina","family":"Kusmartseva","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8489-4782","authenticated-orcid":false,"given":"Mark","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA"},{"name":"Department of Pediatrics, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-5754","authenticated-orcid":false,"given":"Dirk","family":"Homann","sequence":"additional","affiliation":[{"name":"Marc and Jennifer Lipschultz Precision Immunology Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY 10029, USA"},{"name":"Diabetes, Obesity & Metabolism Institute, Department of Medicine, ISMMS, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041123315068000_2025.03.18.644000v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"2026041123315068000_2025.03.18.644000v1.2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142242"},{"key":"2026041123315068000_2025.03.18.644000v1.3","unstructured":"Redondo, M.J. , Onengut-Gumuscu, S. , and Gaulton, K.J. 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