Fig. 1

A high-content screen identifies propargite as a compound that induces pancreatic β-cell death. a Scheme of pancreatic β-cell differentiation and high-content chemical screen. b Chemical structure of two hit compounds: Propargite and Vacor. c Inhibitory curve and IC₅₀ of propargite or Vacor on INS⁺ and INS⁻ cells (n = 8). d, e Immunocytochemistry analysis (d) and survival rate (e) of H1-derived glucose-responding INS⁺ and INS⁻ cells treated with different doses of propargite (n = 8). Pancreatic β-like cells were stained for INS (green) and all cells were counterstained by DAPI (blue). Scale bars, 100 μm. The survival rate was calculated by dividing the average number of cells in propargite-treated conditions by the average number of cells in the DMSO control. f, g Representative live images (f) and fold-change (g) of INS^w/GFP HES3-derived INS-GFP⁺ cells treated with 1.6 μM propargite or DMSO control at different time points compared to initial time 0 (n = 3). Scale bars, 100 μm. h, i, j Representative images (h) and cell survival rate (i) or cell death rate (j) of DMSO or propargite-treated human primary islets (n = 3). Pancreatic β-cells were stained with the INS antibody (green) and dead cells were stained with propidium iodide (PI) (red). Scale bars, 200 μm. Scale bars for higher resolution (Zoom) images, 800 μm. Pancreatic β-cell death rate was calculated by defining percentages of INS⁺ PI⁺ cells in INS⁺ cells, and non-β-cell death rate was calculated by percentages of INS⁻PI⁺ cells in INS⁻ cells. Values presented as mean ± S.D. n.s. indicates a non-significant difference. p values calculated by unpaired two-tailed Student’s t-test were *p < 0.05, ***p < 0.001. Related to Supplementary Fig. 1