PT - JOURNAL ARTICLE AU - Maria Fasolino AU - Gregory W. Schwartz AU - Maria L. Golson AU - Yue J. Wang AU - Ashleigh Morgan AU - Chengyang Liu AU - Jonathan Schug AU - Jinping Liu AU - Minghui Wu AU - Daniel Traum AU - Ayano Kondo AU - Catherine L. May AU - Naomi Goldman AU - Wenliang Wang AU - the HPAP Consortium AU - Michael Feldman AU - Jason H. Moore AU - Alberto S. Japp AU - Michael R. Betts AU - Robert B. Faryabi AU - Ali Naji AU - Klaus H. Kaestner AU - Golnaz Vahedi TI - Multiomics single-cell analysis of human pancreatic islets reveals novel cellular states in health and type 1 diabetes AID - 10.1101/2021.01.28.428598 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.01.28.428598 4099 - http://biorxiv.org/content/early/2021/01/31/2021.01.28.428598.short 4100 - http://biorxiv.org/content/early/2021/01/31/2021.01.28.428598.full AB - Type 1 diabetes (T1D) is an autoimmune disease of only partially defined etiology in which immune cells destroy insulin-producing beta cells. Using single-cell transcriptomics and an advanced analytical strategy to assess pancreatic islets of T1D, autoantibody-positive, and non-diabetic organ donors, we identified both canonical cell types and rare insulin-expressing cells with a hybrid mixture of endocrine and exocrine gene signatures within all donors. We further found elevated expression of MHC Class II pathway genes in exocrine ductal cells of T1D donors, which we confirmed through CyTOF, in situ imaging mass cytometry, and immunofluorescence analysis. Taken together, our multimodal analyses identify novel cell types and processes that may contribute to T1D immunopathogenesis and provide new cellular and molecular insights into human pancreas function.Competing Interest StatementThe authors have declared no competing interest.