Poster #100, City of Hope
Endothelial AGO1 Knockout Promotes Pancreatic Progenitor Cell Regeneration in Diabetic Islets
Mentors: Xuejing Liu, PhD, Sofia Hernandez Corona, BS, PI: Zhen Bouman Chen, PhD
Type 1 diabetes is characterized by the immune system destroying insulin-producing beta cells within pancreatic islets. Endothelial cells (ECs) control critical immune, inflammatory, and regenerative signaling in islets. Our previous work shows Argonaute 1 (AGO1), an RNA-binding protein, regulates EC function in obesity and type 2 diabetes. Preliminary data suggest EC-specific AGO1 knockout (EC-AGO1-KO) protects pancreatic islets under streptozotocin-induced hyperglycemia. However, how EC-AGO1-KO affects pancreatic progenitor cells (i.e., abundance, attributes, EC communication) remains unclear. To address this, we analyzed islet scRNA-seq data from diabetic EC-AGO1-KO mice and their wildtype littermates. Pancreatic progenitor cells from EC-AGO1-KO mice show upregulated cell communication as well as proliferation genes, and downregulated inflammatory response genes, suggesting that EC-AGO1-KO may enhance a progenitor-associated adaptive response during diabetic injury. This study may provide novel insights that support EC AGO1 as a potential therapeutic target for islet regeneration in diabetes.