Fig. 1.

Cell-autonomous oscillators in human pancreatic islets. (a) Bmal1-luc and CMV-GFP co-expression in whole islets. Whole islets were co-transduced with lentiviral particles expressing Bmal1-luc and CMV-GFP constructs. Four days after infection, GFP expression evaluation was performed in n = 20 islets from two donors (ten islets from each donor). At least half of the cells were GFP positive in all visualised islets (representative CMV-GFP transduced islet is shown). (b) Bmal1-luc oscillation profile in synchronised islets. Islets were synchronised with dexamethasone and Bmal1-luc bioluminescence was recorded using an Actimetric Lumicycler for 200 h. Bmal1-luc oscillation profiles were recorded for three parallel dishes for each donor, total of five donors. (c, d) Individual islet circadian bioluminescence recording (ESM Video 1, left). Human islets were cultured on 804G matrix-covered dishes and transduced with Bmal1-luc viral particles. (c) Differential interference contrast (DIC) image. (d) Bioluminescence channel from the time-lapse microscopy images. (e) Trajectories of seven individual islets image by adapted CGE application (image corresponds to ESM Video 1, right). (f) Representative individual islet profile: the raw data (red curve) and the fitted sinusoid (black curve) are shown