Antibody labeling and image acquisition Four to eight μm FFPE sections were stained with an antibody cocktail (Table S1) containing all antibodies. Briefly, tissue sections were de-paraffinized with xylene and carried through sequential rehydration from 100% Ethanol to 70% Ethanol before being transferred to PBS. Heat-induced antigen retrieval was performed in a decloaking chamber (Biocare Medical) at 95°C for 30 min in Tris/EDTA buffer (10mM Tris, 1mM EDTA, pH9.2). Slides were cooled to room temperature (RT) and were subsequently blocked with PBS+3%BSA for 1h at RT. Meanwhile, the antibody cocktail was prepared in PBS+1%BSA buffer, with the appropriate dilution for each of the antibodies (Table S1). Each slide was incubated with 100 μl of the antibody cocktail overnight at 4°C. The next day, slides were washed 3 times with PBS and labeled with 1:400 dilution of Intercalator-Ir (Fluidigm 201192B) in PBS for 30 min at RT. Slides were briefly washed with H2O three times and air dried for at least 30 minutes before IMC acquisition. The IMC was purchased from Fluidigm (Fluidigm, Hyperion Imaging System™). All IMC operation was performed following Fluidigm’s operation procedure. Briefly, following daily tuning of IMC, image acquisition was carried out following manufacturer’s instruction at a laser frequency of 200 Hz. 1000 μm x 1000 μm regions around islets were selected based on bright field images.