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Article History

Received: 17 December 2024

Accepted: 28 January 2025

First Online: 18 March 2025

Acknowledgements

: The secretarial help of A. Mechini and M. Prencipe was highly appreciated. BioRender.com images tool was used to generate the Graphical abstract.

: Raw and analysed data are available from the corresponding author upon request.

: This work is supported by the European Union (EU) within the Italian Ministry of University and Research (MUR) PNRR ‘National Center for Gene Therapy and Drugs based on RNA Technology’ (Project No. CN00000041 CN3 Spoke #5 ‘Inflammatory and Infectious Diseases’), and by the Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement No.115797 INNODIA and No.945268 INNODIA HARVEST. This joint undertaking receives support from the Union’s Horizon 2020 research and innovation programme and EFPIA, Breakthrough T1D (former JDRF) and The Leona M. and Harry B. Helmsley Charitable Trust). The work is also supported by the Italian Ministry of Health through ‘Bando Ricerca Finalizzata 2018’ GR-2018-12365577: ‘The study of human pancreatic islet cell plasticity to predict diabetes onset, progression and personalize therapy’. GS, AP and TM are supported by the Italian Ministry of University and Research (PNRR-PRIN2022 No. P2022EB5B8 and PRIN2022 No.2022FRBXHY). GS is supported by the University of Siena within F-CUR funding program Grant No. 2268-2022-SG-PSR2021-FCUR_001. FD was supported by the Italian Ministry of University and Research with the project PNC 0000001 D3 4 Health, the National Plan for Complementary Investments to the NRRP, funded by the NextGenerationEU, and by the Italian Ministry of Health 'Multidisciplinary and Interregional Hub for Research and Clinical Experimentation To Combat Pandemics and Antibiotic Resistance' (project T4-AN-07, PAN-HUB).

: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: SA, EA and GEG contributed to the conceptualisation, supervision and coordination of the study, the design of the methodology, conducted the investigation and implemented the bioinformatics and statistical analysis, composed the figures and wrote and reviewed the manuscript. DF, GL, AMo, AFB, EP, LN and CF conducted the experiments and the analyses and interpreted the data. MB contributed to the design of the methodology. CG contributed to the investigation and to the design of the methodology. GQ and VT contributed to the investigation and to the design of the methodology. GDG, LS and GC contributed to the investigation and to the design of the methodology. AMa contributed to the investigation. AG and TM contributed to the investigation, to the design of the methodology and helped acquire funding for the research. AP contributed to the investigation to the design of the methodology and helped acquire funding for the research. RR contributed to the investigation and to the design of the methodology. FD and GS contributed to the conceptualisation, supervision and coordination of the study and the design of the methodology, wrote and reviewed the manuscript and helped acquire funding for the research. FD and GS are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of their analysis. All authors substantially contributed to the conception or design of the work, or acquisition, analysis or interpretation of data of the work. All authors critically reviewed the manuscript and approved the final version.