Thursday September 23, 2021 - 17:05 to 17:40
Single-cell landscape of syngeneic and allogeneic islet grafts in diabetic mice
Lisha Mou1, Pengfei Chen2, Yuanzheng Peng1, Ying Lu1, Jiao Chen1, Zijing Wu1, Zuhui Pu1, Zhiming Cai1, Yifan Dai3.
1Shenzhen Xenotransplantation Medical Engineering Research and Development Center, Shenzhen Second People's Hospital, Shenzhen, People's Republic of China; 2Department of Traumatic Orthopedics, Shenzhen Longhua District Central Hospital, Shenzhen, People's Republic of China; 3Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, People's Republic of China
Islet transplantation play an important role in the treatment of type 1 diabetes mellitus. Despite previous discoveries regarding the important roles of the T cells and macrophages in islet graft fate, the microenvironment of islet graft is poorly characterized. In this study, we generated diabetic C57BL/6 mice with streptozotocin. Then syngeneic and allogeneic transplantations were performed under the kidney capsule of the diabetic mice without immunosuppression (recipient C57BL/6 diabetic mice transplanted with islets from C57BL/6 mice or BALB/c mice). All mice remained normoglycemic throughout the study. The grafts (syngeneic, n=4 and allogeneic islet grafts, n=3) were harvested and digested into single cells at 8 days post-transplant. We then profiled the transcriptomes of islet grafts using single-cell RNA sequencing technologies. Based on our data, the cellular composition revealed the following populations of cells: T cells, macrophages, dendritic cells, mesenchyme cells, endothelium cells and islet cells. Our results identified that T cells were abundantly accumulated in allograft, reflecting T cell response as the main immune rejection responses. However, the infiltraion of recipient myeloid cells in allograft was similar to that in syngeneic graft. Importantly, mesenchymal cells are accumulated in syngeneic graft while infrequent in allograft, indicating that the mesenchymal cells may help to maintain the viability of transplanted cells. Collectively, our comprehensive atlas of the islet graft microenvironment provides deeper insights into immune rejection mechanisms associated with the loss function of islets.
We thank Dr. David K.C. Cooper MD (University of Alabama at Birmingham, Birmingham) and Dr. Rita Bottino (Director Islet Programs, Imagine Pharma, Pittsburgh) for helpful discussion and suggestions. Some of the authors of this work were supported in part by grants from the National Key R&D Program of China (2017YFC1103704), Shenzhen High-level Hospital Construction Fund (2019)..