Multiplexed Pan Soluble Ligandome Assaying via OASIS.

ABSTRACT: Screening soluble protein ligands is essential for understanding signaling interactions and enabling drug discovery. Currently, screens require arrayed formats because ligand diffusibility causes non-cell-autonomous effects. To enable multiplexed pooled assaying, we developed Obligate Autocrine Signaling In situ Screening (OASIS). Using lentiviral delivery of genetically barcoded ligands fused to a tethering domain, we anchor proteins to the expressing cell's outer membrane, exclusively enforcing autocrine signaling. Validation using IFNA2 and EGF demonstrated uncompromised autocrine signaling with significantly reduced paracrine activity. We leveraged OASIS to perform a pan-ligandome fitness screen of all 770 validated human ligands in KOLF2.1J hiPSCs, identifying potent self-renewal fact

SUBMITTER: Lee YH 

PROVIDER: S-EPMC12767521 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature