Congrats Meltem!!

Was a really fruitful collaboration Francis!

7/ Overall, this study utilizes a novel method for prioritizing screening targets using omics datasets from SC-beta cells and human islets. We reveal new ways to protect SC-beta cells for type 1 diabetes cell therapy.

6/ We then compared each ligand across multiple doses, and found that the protective effects of FGFs were dose dependent. Of the FGFs, FGF4 the strongest effects across all concentrations tested.

5/ We found that cytokine induction reduced EGFP fluorescence (INS gene activity), and that this effect was also rescued by the FGFs.

4/ We found that of ~150 ligands screened, members of the fibroblast growth factor family had strong protective effects against cytokine-induced SC-beta cell death, in particular FGF4, FGF5, FGF8F, FGF19, and FGF21.

3/ We then screened the ligands in this prioritized list by analyzing cell death using propidium iodide and insulin production using an INS-EGFP reporter that was knocked-in to the stem cells.

2/ Basically, our selection criteria focused on ligand-receptor pairs with ‘sparse’ ligands but available receptors in SC-beta cells compared to human islets.

1/ We combined data from multiple bulk RNAseq, scRNAseq, and proteomics datasets from late stage stem cell-derived beta-cells (SC-beta) and human islets, and leverage this to generate a list of prioritized ligands for a medium throughput screen.

0/ This was a collaborative effort from @jimjohnsonsci.bsky.social @nictitate.bsky.social @wywywa.bsky.social labs.