Large-scale electron microscopy database for human type 1 diabetes

• Published in: Nature communications 2020-05, Vol.11 (1), p.2475-2475, Article 2475
• Main Authors: de Boer, Pascal, Pirozzi, Nicole M., Wolters, Anouk H. G., Kuipers, Jeroen, Kusmartseva, Irina, Atkinson, Mark A., Campbell-Thompson, Martha, Giepmans, Ben N. G.
• Format: Article
• Language: English
• Subjects: 14/28; 14/63; 631/1647/245; 631/250/38; Abnormalities; Anomalies; Autoantibodies - metabolism; Autoimmunity; Beta cells; Cellular stress response; Cytoplasmic Granules - ultrastructure; Data mining; Databases as Topic; Destruction; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - pathology; Electron microscopy; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - ultrastructure; Granule cells; Granulocytes - immunology; Humanities and Social Sciences; Humans; Immune system; Immunity, Innate; Islets of Langerhans - immunology; Islets of Langerhans - pathology; Islets of Langerhans - ultrastructure; Macromolecules; Microscopy; Microscopy, Electron; Mitochondria - metabolism; Mitochondria - ultrastructure; multidisciplinary; Organ donors; Pancreas; Proenzymes; Science; Science (multidisciplinary); Tissue Donors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16287-5

Autoimmune β-cell destruction leads to type 1 diabetes, but the pathophysiological mechanisms remain unclear. To help address this void, we created an open-access online repository, unprecedented in its size, composed of large-scale electron microscopy images (‘nanotomy’) of human pancreas tissue obtained from the Network for Pancreatic Organ donors with Diabetes (nPOD; www.nanotomy.org ). Nanotomy allows analyses of complete donor islets with up to macromolecular resolution. Anomalies we found in type 1 diabetes included (i) an increase of ‘intermediate cells’ containing granules resembling those of exocrine zymogen and endocrine hormone secreting cells; and (ii) elevated presence of innate immune cells. These are our first results of mining the database and support recent findings that suggest that type 1 diabetes includes abnormalities in the exocrine pancreas that may induce endocrine cellular stress as a trigger for autoimmunity. Type 1 diabetes is associated with autoimmune destruction of pancreatic beta-cells. Here the authors compose a large-scale electron microscopy image data base of pancreatic organ donor tissue to enable data mining and further understanding of the disease.