A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Evolving epigenomics of immune cells at single-nucleus resolution in children en route to type 1 diabetes
Tekijät: Pastinen, Tomi; Grundberg, Elin; Bradley, Todd; Honkanen, Jarno; Cheung, Warren A.; Vuorela, Arja; Johnston, Jeffrey J.; Yoo, Byunggil; Khanal, Santosh; McLennan, Rebecca; Ilonen, Jorma; Vaarala, Outi; Krischer, Jeffrey P.; Knip, Mikael
Kustantaja: Springer Science and Business Media LLC
Julkaisuvuosi: 2026
Lehti: Nature Communications
Artikkelin numero: 3168
Vuosikerta: 17
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-026-69923-x
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Kokonaan avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1038/s41467-026-69923-x
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/515791109
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
The appearance of diabetes-associated autoantibodies is the first detectable sign of the disease process leading to type 1 diabetes (T1D). Evidence suggests that T1D is a heterogenous disease, where the type of antibodies first formed implies subtypes. Here, we leverage longitudinal samples collected from 98 European TRIGR participants (49 children who subsequently presented with T1D, and 49 matched controls), and profile single-cell epigenomics at different time points of disease development. Quantitation of cell and nuclei populations, complemented by analysis of transcriptome and open-chromatin states, indicates robust, early, replicable monocyte lineage differences between cases and controls, suggesting the early emergence of heightened pro-inflammatory cytokine secretion among cases. The order of autoantibody emergence in cases shows variation across lymphoid and myeloid cells, potentially indicating divergence in the cellular immune response. The strong monocytic lineage representation in peripheral blood immune cells before seroconversion and the weaker differential coordination of these gene networks close to clinical diagnosis emphasize the importance of early life as a critical phase in T1D development.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
T.P. holds a Fred and Dee Lyons Endowed Chair in Pediatric Genomic Medicine. Grant support for the study was from Academy of Finland (grant 350455) to M.K. The authors thank the TRIGR Study Group for making the PBMC samples available from the TRIGR children analyzed in this study. The TRIGR study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (grants HD040364, HD042444 and HD051997), Canadian Institutes of Health Research, JDRF and the Commission of the European Communities (specific RTD program “Quality of Life and management of Living Resources”, contract number QLK1-2002-00372 “Diabetes Prevention”) and the EFSD/JDRF/Novo Nordisk Focused Research Grant.
