Stage-specific transcriptomic changes in pancreatic α-cells after massive β-cell loss

BMC Genomics

Santiago A. Rodríguez-Seguí¹  Agustín Romero¹  Daniel Oropeza²  Pedro L. Herrera²  Simona Chera³  Valentina Cigliola⁴ 

[1] Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), CONICET-Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina;Department of Genetic Medicine and Development, iGE3 and Centre Facultaire du Diabète, Faculty of Medicine, University of Geneva, Geneva, Switzerland;Department of Genetic Medicine and Development, iGE3 and Centre Facultaire du Diabète, Faculty of Medicine, University of Geneva, Geneva, Switzerland;Department of Clinical Science, Center for Diabetes Research, Faculty of Medicine, University of Bergen, Bergen, Norway;Department of Genetic Medicine and Development, iGE3 and Centre Facultaire du Diabète, Faculty of Medicine, University of Geneva, Geneva, Switzerland;Present address: Department of Cell Biology, Duke University Medical Center, Durham, NC, USA;Regeneration Next, Duke University, 27710, Durham, North Carolina, USA;

关键词: Alpha cell;    Beta cell;    Pancreas;    Pancreatic islet;    Conversion;    RNA-seq;    Transcriptome;    Plasticity;    Regeneration;    Ifit3;   

DOI  :  10.1186/s12864-021-07812-x

来源: Springer

【 摘 要 】

BackgroundLoss of pancreatic insulin-secreting β-cells due to metabolic or autoimmune damage leads to the development of diabetes. The discovery that α-cells can be efficiently reprogrammed into insulin-secreting cells in mice and humans has opened promising avenues for innovative diabetes therapies. β-cell loss triggers spontaneous reprogramming of only 1–2% of α-cells, limiting the extent of regeneration. Most α-cells are refractory to conversion and their global transcriptomic response to severe β-cell loss as well as the mechanisms opposing their reprogramming into insulin producers are largely unknown. Here, we performed RNA-seq on FAC-sorted α-cells to characterize their global transcriptional responses at different time points after massive β-cell ablation.ResultsOur results show that α-cells undergo stage-specific transcriptional changes 5- and 15-days post-diphtheria toxin (DT)-mediated β-cell ablation. At 5 days, α-cells transiently upregulate various genes associated with interferon signaling and proliferation, including Interferon Induced Protein with Tetratricopeptide Repeats 3 (Ifit3). Subsequently, at 15 days post β-cell ablation, α-cells undergo a transient downregulation of genes from several pathways including Insulin receptor, mTOR and MET signaling.ConclusionsThe results presented here pinpoint novel markers discriminating α-cells at different stages after acute β-cell loss, and highlight additional signaling pathways that are modulated in α-cells in this context.

【 授权许可】

CC BY