Latent Regulatory Programs Generate Synthetic T Cell States with Enhanced Therapeutic Potential.

ABSTRACT: Transcription factors (TFs) govern cell fate through coordinated gene-regulatory networks, yet the full potential of these networks to generate non-native, therapeutically advantageous cell states in vivo remains largely unexplored. We hypothesized that systematic gain-of-function (GOF) overexpression of TFs in CD8⁺ T cells, central mediators of immune protection, could reveal latent, or "hidden," regulatory programs capable of generating synthetic T cell states with therapeutic utility. To test this, we developed single-cell GOF sequencing (scGOF-seq), a multiplexed platform for unbiased, in vivo mapping of GOF effects on T cell fate in immunocompetent mouse models of infection and cancer. scGOF-seq uncovered unexpected regulators of T cell differentiation and acc

SUBMITTER: Pratt BM 

PROVIDER: S-EPMC12803213 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature