biostudies-literatureTous CNCATS NIH HHSNIBIB NIH HHSNHLBI NIH HHSNIGMS NIH HHSeadt1971https://www.ebi.ac.uk/biostudies/studies/S-EPMC12063640biostudies-literatureUnknown11(19)Light-inducible regulatory proteins are powerful tools to interrogate fundamental mechanisms driving cellular behavior. In particular, genetically encoded photosensory domains fused to split proteins can tightly modulate protein activity and gene expression. While light-inducible split protein systems have performed well individually, few multichromatic and orthogonal gene regulation systems exist in mammalian cells. The design space for multichromatic circuits is limited by the small number of orthogonally addressable optogenetic switches and the types of effectors that can be actuated by them. We developed a library of red light-inducible recombinases and directed patterned myogenesis in a mesenchymal fibroblast-like cell line. To address the limited number of light-inducible domains (LIScience advancesMultiplexing light-inducible recombinases to control cell fate, Boolean logic, and cell patterning in mammalian cells.PMC12063640F32 HL160194TL1 TR001410R01 EB031904R01 GM129011Rice MELTous CKinstlinger ISDeng JWong WWfalseMultiplexing light-inducible recombinases to control cell fate, Boolean logic, and cell patterning in mammalian cells.Light-inducible regulatory proteins are powerful tools to interrogate fundamental mechanisms driving cellular behavior. In particular, genetically encoded photosensory domains fused to split proteins can tightly modulate protein activity and gene expression. While light-inducible split protein systems have performed well individually, few multichromatic and orthogonal gene regulation systems exist in mammalian cells. The design space for multichromatic circuits is limited by the small number of orthogonally addressable optogenetic switches and the types of effectors that can be actuated by them. We developed a library of red light-inducible recombinases and directed patterned myogenesis in a mesenchymal fibroblast-like cell line. To address the limited number of light-inducible domains (LI2025-01-01T00:00:00Z2025 May2026-07-15T08:28:11.223Z2026-07-01T03:12:10.788ZS-EPMC120636404034405210.1126/sciadv.adt1971