Subpopulations of mouse beta cells

Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune mediated destruction of ß cells. How ß cells respond to immune attack is unknown. We identified a population of ß cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal ß cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of ß cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes. This new subpopulation is resistant to killing when diabetes is precipitated with cyclosphosphamide. Human ß cells show similar changes when cultured with immune cells. These changes may account for the chronicity of the disease and the long term survival of ß cells in some patients. Overall design: mRNA profiles of top and bottom beta cells were generated by RNA-seq. 4 samples were processed from each population of cells.

8

Rui J, Deng S, Arazi A, Perdigoto AL, Liu Z, Herold KC