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

• Autores: Oropeza, Daniel; Cigliola, Valentina; Romero, Agustín; Chera, Simona; Rodríguez Seguí, Santiago Andrés; Herrera, Pedro L.
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ALPHA CELL; BETA CELL; CONVERSION; IFIT3; PANCREAS; PANCREATIC ISLET; PLASTICITY; REGENERATION; RNA-SEQ; TRANSCRIPTOME
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Background: Loss 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. Results: Our 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. Conclusions: The 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.
Fil: Oropeza, Daniel. University Of Geneva (ug);
Fil: Cigliola, Valentina. University Of Geneva (ug);
Fil: Romero, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Chera, Simona. University Of Geneva (ug);
Fil: Rodríguez Seguí, Santiago Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Herrera, Pedro L.. University Of Geneva (ug);