{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:12:14Z","timestamp":1792069934733,"version":"4.4.0"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to destruction of pancreatic <jats:italic>\u03b2<\/jats:italic>-cells and loss of insulin production ability. Pathogenesis of T1DM is a complex process involving different types of immune cells, particularly, T-lymphocytes (including effector cells, Thelpers, regulatory lymphocytes, MAIT cells), B-lymphocytes, natural killers, monocytes, dendritic cells, and other minor cellular populations that form autoimmune response against islet cells. The heterogeneity of intercellular communications in the pancreas and adjacent lymph nodes of patients, as well as diverse functional state of islet cells, make a significant contribution to the pathogenesis of this disease. This makes the detailed consideration of immune cell subpopulations very essential for investigating the pathogenesis of the disease. Understanding the relations between changes of transcriptional activities in different cellular subtypes may allow to study the pathogenetic mechanism of T1DM in more detail, which could further be applied in both diagnostics and treatment. Single-cell RNA sequencing (scRNA-seq) allows to examine the interactions between immune cell subtypes and to identify differentially expressed genes specific for early stages of T1DM in particular cell subtypes. This review summarizes modern studies focusing on application of scRNA-seq for the studies of T1DM pathogenesis, novel biomarkers of manifestation, progression, and treatment efficiency for diabetes and its complications. The review covers studies on different cells and human tissues (endocrine, exocrine and immune pancreatic cells, PBMC) and model animals with experimental T1DM and its complications.<\/jats:p>","DOI":"10.3389\/fendo.2025.1663728","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T04:12:32Z","timestamp":1757045552000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Single-cell RNA sequencing in studies of type 1 diabetes mellitus: modern state-of-the-art and technical peculiarities"],"prefix":"10.3389","volume":"16","author":[{"given":"Azat Vadimovich","family":"Abdullatypov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Valentinovna","family":"Glushkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina Sergeevna","family":"Petriaikina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor Pavlovich","family":"Bogdanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry Vyacheslavovich","family":"Tabakov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilii Eduardovich","family":"Akimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir Sergeevich","family":"Yudin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton Arturovich","family":"Keskinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey Mikhailovich","family":"Yudin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel Yuryevich","family":"Volchkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry Vladimirovich","family":"Svetlichnyy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Woroncow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika Igorevna","family":"Skvortsova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00218-2","article-title":"enGlobal incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study","volume":"10","author":"Gregory","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-023-01520-4","article-title":"enThe T1D index: implications of initial results, data limitations, and future development","volume":"23","author":"Ogle","year":"2023","journal-title":"Curr Diabetes Rep"},{"key":"B3","volume-title":"IDF Diabetes Atlas 2025","author":"Federation","year":"2025"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119220","article-title":"enAdvances in immunotherapeutic approaches to type 1 diabetes","volume":"24","author":"Cudini","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01418-2","article-title":"en100 years of insulin: celebrating the past, present and future of diabetes therapy","volume":"27","author":"Sims","year":"2021","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-017-1033-7","article-title":"enJoint modeling of longitudinal autoantibody patterns and progression to type 1 diabetes: results from the TEDDY study","volume":"54","author":"K\u00f6hler","year":"2017","journal-title":"Acta Diabetologica"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.08.007","article-title":"enImmune and pancreatic cell interactions in type 1 diabetes","volume":"27","author":"Boldison","year":"2016","journal-title":"Trends Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0254-y","article-title":"enThe heterogeneous pathogenesis of type 1 diabetes mellitus","volume":"15","author":"Ilonen","year":"2019","journal-title":"Nat Rev Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jaut.2017.09.012","article-title":"enRisk of beta-cell autoimmunity presence for progression to type 1 diabetes: A systematic review and meta-analysis","volume":"86","author":"Ling","year":"2018","journal-title":"J Autoimmun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00985-4","article-title":"enThe immunology of type 1 diabetes","volume":"24","author":"Herold","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2337\/dc23-0417","article-title":"enHLA genotype and probiotics modify the association between timing of solid food introduction and islet autoimmunity in the TEDDY study","volume":"46","author":"Uusitalo","year":"2023","journal-title":"Diabetes Care"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1101\/2025.02.19.639120","article-title":"enIFN- induces heterogenous ROS production in human -cells","author":"Wagner","year":"2025"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198605223142106","article-title":"Type i diabetes mellitus","volume":"314","author":"Eisenbarth","year":"1986","journal-title":"New Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3892\/br.2024.1770","article-title":"Viruses as a potential environmental trigger of type 1 diabetes mellitus (Review)","volume":"20","author":"Alves Abrantes","year":"2024","journal-title":"Biomed Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3928\/19382359-20240502-07","article-title":"enCOVID-19 and diabetes: an epidemiologic overview","volume":"53","author":"Mannheim","year":"2024","journal-title":"Pediatr Ann"},{"key":"B16","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/imr.13362","article-title":"enCracking the type 1 diabetes code: Genes, microbes, immunity, and the early life environment","volume":"325","author":"Yau","year":"2024","journal-title":"Immunol Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad165","article-title":"enCOVID-19 as a trigger for type 1 diabetes","volume":"108","author":"Wang","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1326711","article-title":"Immunological and virological triggers of type 1 diabetes: insights and implications","volume":"14","author":"Lemos","year":"2024","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1576419","article-title":"Reframing type 1 diabetes through the endocannabinoidome-microbiota axis: a systems biology perspective","volume":"16","author":"\u0141ukowski","year":"2025","journal-title":"Front Endocrinol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/s11892-018-1085-2","article-title":"enThe impact of pancreatic beta cell heterogeneity on type 1 diabetes pathogenesis","volume":"18","author":"Benninger","year":"2018","journal-title":"Curr Diabetes Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087630","article-title":"enA concerted vision to advance the knowledge of diabetes mellitus related to immune checkpoint inhibitors","volume":"24","author":"Deligiorgi","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-023-00826-3","article-title":"enWhy does the immune system destroy pancreatic-cells but not -cells in type 1 diabetes","volume":"19","author":"Eizirik","year":"2023","journal-title":"Nat Rev Endocrinol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.cmet.2018.11.014","article-title":"enA map of human type 1 diabetes progression by imaging mass cytometry","volume":"29","author":"Damond","year":"2019","journal-title":"Cell Metab"},{"key":"B24","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1186\/s13098-024-01549-9","article-title":"enAnalysis of frequency changes in CD8+ regulatory T cell subsets in peripheral blood of individuals with type 1 diabetes","volume":"16","author":"Chen","year":"2024","journal-title":"Diabetol Metab Syndrome"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0633-5","article-title":"enBeta cell-specific CD8+ T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes","volume":"21","author":"Abdelsamed","year":"2020","journal-title":"Nat Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1377322","article-title":"EnglishAutoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection","volume":"15","author":"Yang","year":"2024","journal-title":"Front Endocrinol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0006","article-title":"enB-cell cross-presentation of autologous antigen precipitates diabetes","volume":"61","author":"Mari\u00f1o","year":"2012","journal-title":"Diabetes"},{"key":"B28","doi-asserted-by":"publisher","first-page":"67","DOI":"10.5114\/pg.2021.104737","article-title":"Low-dose interleukin2-loaded nanoparticle effect on NK and T-reg cell expression in experimentally induced type 1 diabetes mellitus","volume":"16","author":"Aboelnazar","year":"2021","journal-title":"Gastroenterol Rev"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S470738","article-title":"engIdentification of immune gene signature associated with T cells and natural killer cells in type 1 diabetes","volume":"17","author":"Wang","year":"2024","journal-title":"Diabetes Metab Syndrome Obesity: Targets Ther"},{"key":"B30","doi-asserted-by":"publisher","first-page":"eadn2136","DOI":"10.1126\/sciadv.adn2136","article-title":"enMonocytes in type 1 diabetes families exhibit high cytolytic activity and subset abundances that correlate with clinical progression","volume":"10","author":"Pant","year":"2024","journal-title":"Sci Adv"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16384","article-title":"enSingle-cell transcriptional profiling reveals cellular senescence and inflammatory persistence as key features of type 1 diabetes partial remission","volume":"27","author":"Xie","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.153136","article-title":"enEvidence of islet CADM1-mediated immune cell interactions during human type 1 diabetes","volume":"7","author":"Sona","year":"2022","journal-title":"JCI Insight"},{"key":"B33","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s40104-024-01063-y","article-title":"enAdvances in singlecell transcriptomics in animal research","volume":"15","author":"Yan","year":"2024","journal-title":"J Anim Sci Biotechnol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1155\/jdr\/3248350","article-title":"enApplication and progression of single-cell RNA sequencing in diabetes mellitus and diabetes complications","volume":"2025","author":"Hong","year":"2025","journal-title":"J Diabetes Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.10","article-title":"enTranslating RNA sequencing into clinical diagnostics: opportunities and challenges","volume":"17","author":"Byron","year":"2016","journal-title":"Nat Rev Genet"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.01152","article-title":"RNA-Seq perspectives to improve clinical diagnosis","volume":"10","author":"Marco-Puche","year":"2019","journal-title":"Front Genet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.06.003","article-title":"enResearch techniques made simple: methodology and clinical applications of RNA sequencing","volume":"136","author":"Whitley","year":"2016","journal-title":"J Invest Dermatol"},{"key":"B38","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-0716-2376-3_19","article-title":"Single-cell rna sequencing analysis using fluidigm c1 platform for characterization of heterogeneous transcriptomes","volume-title":"Cancer Cell Biology: Methods and Protocols","author":"Kim","year":"2022"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2024.103475","article-title":"enProfiling low-mRNA content cells in complex human tissues using BD Rhapsody single-cell analysis","volume":"5","author":"Scheiber","year":"2024","journal-title":"STAR Protoc"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/hem3.149","article-title":"enSingle-cell RNA sequencing of pediatric Hodgkin lymphoma to study the inhibition of T cell subtypes","volume":"8","author":"De Kanter","year":"2024","journal-title":"HemaSphere"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1039\/C8LC01239C","article-title":"enDroplet-based single cell RNAseq tools: a practical guide","volume":"19","author":"Salomon","year":"2019","journal-title":"Lab Chip"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1039\/C7LC90070H","article-title":"enInDrops and Drop-seq technologies for single-cell sequencing","volume":"17","author":"Klein","year":"2017","journal-title":"Lab Chip"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0492-x","article-title":"Gene expression atlas of a developing tissue by single cell expression correlation analysis","volume":"16","author":"Bageritz","year":"2019","journal-title":"Nat Methods"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.853349","article-title":"Single-cell landscape of mouse islet allograft and syngeneic graft","volume":"13","author":"Chen","year":"2022","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2025.108362","article-title":"enA systematic review of single-cell RNA sequencing applications and innovations","volume":"115","author":"Rafi","year":"2025","journal-title":"Comput Biol Chem"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e2404775121","DOI":"10.1073\/pnas.2404775121","article-title":"enCellular heterogeneity and dynamics of the human uterus in healthy premenopausal women","volume":"121","author":"Ulrich","year":"2024","journal-title":"Proc Natl Acad Sci"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-020-00177-1","article-title":"enSinglecell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain","volume":"42","author":"Kiss","year":"2020","journal-title":"GeroScience"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01553","article-title":"Single cell RNA sequencing of rare immune cell populations","volume":"9","author":"Nguyen","year":"2018","journal-title":"Front Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2025.2471568","article-title":"enComprehensive profiling of cell type-specific expression and distribution of complement genes in mouse and human kidneys: insights into normal physiology and response to kidney transplantations","volume":"47","author":"Li","year":"2025","journal-title":"Renal Failure"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1080\/15412555.2024.2444663","article-title":"enThe role of autophagy and cell communication in COPD progression: insights from bioinformatics and scRNA-seq","volume":"22","author":"Ren","year":"2025","journal-title":"COPD: J Chronic Obstructive Pulmonary Dis"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1038\/s41467-025-56323-w","article-title":"enSingle-cell RNA sequencing defines distinct disease subtypes and reveals hypo-responsiveness to interferon in asymptomatic Waldenstrom\u2019s Macroglobulinemia","volume":"16","author":"Sklavenitis-Pistofidis","year":"2025","journal-title":"Nat Commun"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.11.028","article-title":"enSingle-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer","volume":"147","author":"Liu","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-024-06098-4","article-title":"enA novel subpopulation of monocytes with a strong interferon signature indicated by SIGLEC-1 is present in patients with in recent-onset type 1 diabetes","volume":"67","author":"Guo","year":"2024","journal-title":"Diabetologia"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf1970","article-title":"enSingle-cell RNA-seq reveals cell type\u2013specific molecular and genetic associations to lupus","volume":"376","author":"Perez","year":"2022","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.178499","article-title":"enSingle-cell RNA-seq analysis reveals cell subsets and gene signatures associated with Rheumatoid Arthritis Disease Activity","volume":"9","author":"Binvignat","year":"2024","journal-title":"JCI Insight"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0058","article-title":"enNIH initiative to improve understanding of the pancreas, islet, and autoimmunity in type 1 diabetes: the human pancreas analysis program (HPAP)","volume":"68","author":"Kaestner","year":"2019","journal-title":"Diabetes"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108637","article-title":"enAdverse effects of gestational diabetes mellitus on fetal monocytes revealed by single-cell RNA sequencing","volume":"27","author":"Yin","year":"2024","journal-title":"iScience"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1501660","article-title":"Single-cell RNA sequencing reveals the dysfunctional characteristics of PBMCs in patients with type 2 diabetes mellitus","volume":"15","author":"Zhao","year":"2025","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1537909","article-title":"Immunometabolic alterations in type 2 diabetes mellitus revealed by single-cell RNA sequencing: insights into subtypes and therapeutic targets","volume":"15","author":"Li","year":"2025","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101198R","article-title":"enDecoding the role of macrophages in periodontitis and type 2 diabetes using single-cell RNA-sequencing","volume":"36","author":"Agrafioti","year":"2022","journal-title":"FASEB J"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2025.02.018","article-title":"enInterferon regulatory factor 1 promotes diabetic vasculopathy by mediating endothelial cell pyroptosis","volume":"115","author":"Zhou","year":"2025","journal-title":"Ann Vasc Surg"},{"key":"B62","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s11658-024-00668-5","article-title":"enSingle-cell view and a novel protective macrophage subset in perivascular adipose tissue in T2DM","volume":"29","author":"Li","year":"2024","journal-title":"Cell Mol Biol Lett"},{"key":"B63","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1186\/s40001-023-01321-1","article-title":"enIdentification and validation of core genes for type 2 diabetes mellitus by integrated analysis of single-cell and bulk RNA-sequencing","volume":"28","author":"Yang","year":"2023","journal-title":"Eur J Med Res"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-023-01942-y","article-title":"enSingle-cell RNA sequencing reveals RAC1 involvement in macrophages efferocytosis in diabetic kidney disease","volume":"47","author":"Song","year":"2024","journal-title":"Inflammation"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00531-x","article-title":"enSingle-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes","volume":"4","author":"Fasolino","year":"2022","journal-title":"Nat Metab"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e36524","article-title":"enBiological function of type 1 regulatory cells and their role in type 1 diabetes","volume":"10","author":"Qi","year":"2024","journal-title":"Heliyon"},{"key":"B67","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.140.8.2569","article-title":"engT cell autoreactivity to insulin in diabetic and related non-diabetic individuals","volume":"140","author":"Naquet","year":"1988","journal-title":"J Immunol (Baltimore Md.: 1950)"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/0198-8859(93)90128-N","article-title":"enAutoreactive T cells from a type I diabetic recognize multiple class II products","volume":"36","author":"Miller","year":"1993","journal-title":"Hum Immunol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13073-024-01300-z","article-title":"enSystematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes","volume":"16","author":"Honardoost","year":"2024","journal-title":"Genome Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107433","article-title":"enTargeting the autoreactive CD8+ T-cell receptor in type 1 diabetes: Insights from scRNA-seq for immunotherapy","volume":"209","author":"Lai","year":"2024","journal-title":"Pharmacol Res"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700172","article-title":"enSingle-cell RNA sequencing reveals expanded clones of islet antigen-reactive CD4+ T cells in peripheral blood of subjects with type 1 diabetes","volume":"199","author":"Cerosaletti","year":"2017","journal-title":"J Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3390\/cells11101623","article-title":"enCharacterization of peripheral blood TCR in patients with type 1 diabetes mellitus by BD rhapsodyTM VDJ CDR3 assay","volume":"11","author":"Okamura","year":"2022","journal-title":"Cells"},{"key":"B73","doi-asserted-by":"publisher","first-page":"9204","DOI":"10.1038\/s41467-024-53255-9","article-title":"enPhysiological and pathogenic T cell autoreactivity converge in type 1 diabetes","volume":"15","author":"Eugster","year":"2024","journal-title":"Nat Commun"},{"key":"B74","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3164\/jcbn.24-86","article-title":"enSingle-cell analysis reveals islet autoantigen\u2019s immune activation in type 1 diabetes patients","volume":"76","author":"Okamura","year":"2025","journal-title":"J Clin Biochem Nutr"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0932778100","article-title":"enIdentification of the cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes","volume":"100","author":"Lieberman","year":"2003","journal-title":"Proc Natl Acad Sci"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-024-06341-y","article-title":"enSingle-cell RNA sequencing identifies endothelial-derived HBEGF as promoting pancreatic beta cell proliferation in mice via the EGFR\u2013Kmt5a\u2013H4K20me pathway","volume":"68","author":"Lai","year":"2025","journal-title":"Diabetologia"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04248-x","article-title":"enAn autoimmune stem-like CD8 T cell population drives type 1 diabetes","volume":"602","author":"Gearty","year":"2022","journal-title":"Nature"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1370907","article-title":"TIGIT acts as an immune checkpoint upon inhibition of PD1 signaling in autoimmune diabetes","volume":"15","author":"Trivedi","year":"2024","journal-title":"Front Immunol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1125605","article-title":"Regulation of CD8 T cell by B-cells: A narrative review","volume":"14","author":"Van Meerhaeghe","year":"2023","journal-title":"Front Immunol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/6581213","article-title":"enThe multiple roles of B lymphocytes in the onset and treatment of type 1 diabetes: interactions between B lymphocytes and T cells","volume":"2021","author":"Xiao","year":"2021","journal-title":"J Diabetes Res"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115425","article-title":"enActivated polyreactive B cells are clonally expanded in autoantibody positive and patients with recent-onset type 1 diabetes","volume":"44","author":"Nicholas","year":"2025","journal-title":"Cell Rep"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.105593","article-title":"enTCL1A in na\u00efve B cells as a therapeutic target for type 1 diabetes","volume":"113","author":"Luo","year":"2025","journal-title":"eBioMedicine"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2022.01.006","article-title":"enSingle-cell RNA sequencing analysis reveals the relationship of bone marrow and osteopenia in STZ-induced type 1 diabetic mice","volume":"41","author":"Zhong","year":"2022","journal-title":"J Advanced Res"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.961209","article-title":"Comparative analysis of the repertoire of insulin-reactive B cells in type 1 diabetes-prone and resistant mice","volume":"13","author":"Banach","year":"2022","journal-title":"Front Immunol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192362","article-title":"enSingle-cell RNA sequencing of murine islets shows high cellular complexity at all stages of autoimmune diabetes","volume":"217","author":"Zakharov","year":"2020","journal-title":"J Exp Med"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1101\/2024.12.12.628291","article-title":"enImmune mechanisms of type 1 diabetes revealed by single-cell transcriptomics, bulk transcriptomics, and experimental validation","author":"Gao","year":"2024"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1002\/art.40793","article-title":"enAssociation of dendritic cell signatures with autoimmune inflammation revealed by single-cell profiling","volume":"71","author":"Ashton","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.807632","article-title":"Pancreas\u2014Its functions, disorders, and physiological impact on the mammals\u2019 Organism","volume":"13","author":"Karpi\u0144ska","year":"2022","journal-title":"Front Physiol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00317-7","article-title":"enMechanisms controlling pancreatic islet cell function in insulin secretion","volume":"22","author":"Campbell","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2022.0324","article-title":"enHeterogeneity of islet cells during embryogenesis and differentiation","volume":"47","author":"Sasaki","year":"2023","journal-title":"Diabetes Metab J"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05699-1","article-title":"enLessons from single-cell RNA sequencing of human islets","volume":"65","author":"Ngara","year":"2022","journal-title":"Diabetologia"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1016\/j.cmet.2020.04.005","article-title":"enPatch-seq links single-cell transcriptomes to human islet dysfunction in diabetes","volume":"31","author":"Camunas-Soler","year":"2020","journal-title":"Cell Metab"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0405","article-title":"enSingle-cell transcriptomics of the human endocrine pancreas","volume":"65","author":"Wang","year":"2016","journal-title":"Diabetes"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01179-2","article-title":"enSinglenucleus RNA sequencing of human pancreatic islets identifies novel gene sets and distinguishes cell subpopulations with dynamic transcriptome profiles","volume":"15","author":"Kang","year":"2023","journal-title":"Genome Med"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01380-2","article-title":"enSPOCK2 controls the proliferation and function of immature pancreatic -cells through MMP2","volume":"57","author":"Blaszczyk","year":"2025","journal-title":"Exp Mol Med"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1101\/2024.02.24.581864","article-title":"enMetabolic control of adaptive -cell proliferation by the protein deacetylase SIRT2","author":"Wortham","year":"2024"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.018","article-title":"enThe pathogenic \u201csymphony\u201d in type 1 diabetes: A disorder of the immune system, cells, and exocrine pancreas","volume":"35","author":"Atkinson","year":"2023","journal-title":"Cell Metab"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc5586","article-title":"enThe healthy exocrine pancreas contains preproinsulin-specific CD8 T cells that attack islets in type 1 diabetes","volume":"6","author":"Bender","year":"2020","journal-title":"Sci Adv"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-024-01961-7","article-title":"enUsing geoMx DSP spatial proteomics to investigate immune infiltration of NOD mouse islet and exocrine compartments","volume":"26","author":"Tekin","year":"2024","journal-title":"Mol Imaging Biol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1750-x","article-title":"enImpaired glucagon secretion in patients with fulminant type 1 diabetes mellitus","volume":"63","author":"Komada","year":"2019","journal-title":"Endocrine"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16409","article-title":"enRecurrent hypoglycaemia leads to impairment in glucagon-mediated hepatic glycogenolysis in type 1 diabetic mice","volume":"27","author":"Li","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v16.i2.99928","article-title":"Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes","volume":"16","author":"Rocha","year":"2025","journal-title":"World J Diabetes"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.115225","article-title":"enChronic intermittent fasting impairs cell maturation and function in adolescent mice","volume":"44","author":"Matta","year":"2025","journal-title":"Cell Rep"},{"key":"B104","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/s42255-020-0171-3","article-title":"enTargeted pharmacological therapy restores -cell function for diabetes remission","volume":"2","author":"Sachs","year":"2020","journal-title":"Nat Metab"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1172\/JCI156243","article-title":"en Cell dysfunction in islets from nondiabetic, glutamic acid decarboxylase autoantibody\u2013positive individuals","volume":"132","author":"Doliba","year":"2022","journal-title":"J Clin Invest"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.2337\/db23-0911","article-title":"enElevated cathepsin S serum levels in new-onset type 1 diabetes and autoantibody-positive siblings","volume":"73","author":"Fr\u00f8rup","year":"2024","journal-title":"Diabetes"},{"key":"B107","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/s41419-024-06583-z","article-title":"enSingle-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis","volume":"15","author":"Guo","year":"2024","journal-title":"Cell Death Dis"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0287","article-title":"enEarly detection of peripheral blood cell signature in children developing -cell autoimmunity at a young age","volume":"68","author":"Kallionp\u00e4\u00e4","year":"2019","journal-title":"Diabetes"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1172\/JCI177492","article-title":"enTeplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes","volume":"134","author":"Lled\u00f3-Delgado","year":"2024","journal-title":"J Clin Invest"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.2337\/db21-0426","article-title":"enEndosomal sequestration of TLR4 antibody induces myeloid-derived suppressor cells and reverses acute type 1 diabetes","volume":"71","author":"Locker","year":"2022","journal-title":"Diabetes"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.167881","article-title":"enIsletautoreactive CD4+ T cells are linked with response to alefacept in type 1 diabetes","volume":"8","author":"Balmas","year":"2023","journal-title":"JCI Insight"},{"key":"B112","author":"Sun","year":"2024"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108067","article-title":"enSingle-cell transcriptome profiling reveals cell maturation in stem cell-derived islets after transplantation","volume":"32","author":"Augsornworawat","year":"2020","journal-title":"Cell Rep"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1101\/2024.11.19.624394","article-title":"enControlling human stem cell-derived islet composition using magnetic sorting","author":"Kelley","year":"2024"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0263005","article-title":"enCryopreservation and post-thaw characterization of dissociated human islet cells","volume":"17","author":"Marquez-Curtis","year":"2022","journal-title":"PloS One"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101832","article-title":"enCycling alpha cells in regenerative drug-treated human pancreatic islets may serve as key beta cell progenitors","volume":"5","author":"Karakose","year":"2024","journal-title":"Cell Rep Med"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.02.014","article-title":"enLong-term correction of diabetes in mice by in vivo reprogramming of pancreatic ducts","volume":"26","author":"Wang","year":"2018","journal-title":"Mol Ther"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1407118","article-title":"Exploring the molecular mechanisms of macrophages in islet transplantation using single-cell analysis","volume":"15","author":"Pu","year":"2024","journal-title":"Front Immunol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1429205","article-title":"Elucidating T cell dynamics and molecular mechanisms in syngeneic and allogeneic islet transplantation through single-cell RNA sequencing","volume":"15","author":"Zhou","year":"2024","journal-title":"Front Immunol"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202100265","article-title":"enIn-depth analysis of proteomic and genomic fluctuations during the time course of human embryonic stem cells directed differentiation into beta cells","volume":"22","author":"Budnik","year":"2022","journal-title":"PROTEOMICS"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0430-6","article-title":"enTargeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells","volume":"38","author":"Hogrebe","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1261\/rna.078154.120","article-title":"enSingle-cell transcriptome sequencing on the Nanopore platform with ScNapBar","volume":"27","author":"Wang","year":"2021","journal-title":"RNA"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.798316","article-title":"Single-cell RNA sequencing profiles identify important pathophysiologic factors in the progression of diabetic nephropathy","volume":"10","author":"Lu","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-022-00707-w","article-title":"enSingle-cell RNA-Seq analysis of diabetic wound macrophages in STZ-induced mice","volume":"17","author":"Ma","year":"2023","journal-title":"J Cell Communication Signaling"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.856299","article-title":"The development of mechanical allodynia in diabetic rats revealed by single-cell RNA-seq","volume":"15","author":"Zhou","year":"2022","journal-title":"Front Mol Neurosci"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108718","article-title":"enSingle cell RNA sequencing (scRNA-Seq) deciphering pathological alterations in streptozotocin-induced diabetic retinas","volume":"210","author":"Sun","year":"2021","journal-title":"Exp Eye Res"},{"key":"B127","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.jcjd.2021.03.007","article-title":"enA New Hypothesis for Type 1 Diabetes Risk: The At-Risk Allele at rs3842753 Associates With Increased Beta-Cell INS Messenger RNA in a Meta-Analysis of Single-Cell RNA-Sequencing Data","volume":"45","author":"Wang","year":"2021","journal-title":"Can J Diabetes"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2025.149412","article-title":"enSRSF10 regulates isoform expression of transcripts associated with proliferative diabetes retinopathy in ARPE-19 cells based on long-read RNA and immunoprecipitation sequencing","volume":"957","author":"Jin","year":"2025","journal-title":"Gene"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.05.020","article-title":"enSystematic evaluation of single-cell RNA-seq analyses performance based on long-read sequencing platforms","volume":"71","author":"Deng","year":"2025","journal-title":"J Advanced Res"},{"key":"B130","doi-asserted-by":"publisher","first-page":"2631","DOI":"10.1038\/s41467-023-38324-9","article-title":"enHigh-throughput and high-accuracy single-cell RNA isoform analysis using PacBio circular consensus sequencing","volume":"14","author":"Shi","year":"2023","journal-title":"Nat Commun"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1663728\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T04:12:34Z","timestamp":1757045554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1663728\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":130,"alternative-id":["10.3389\/fendo.2025.1663728"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1663728","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,5]]},"article-number":"1663728"}}