Pinpointing molecular regulators of CD8 T cell differentiation through multimodal single-cell profiling

Abstract CD8 T lymphocytes control infection and malignancy through differentiation into specialized cell states with discrete functional attributes. While fate commitment is a transcriptionally epigenetically controlled process, the transcription factors chromatin modifiers governing remain ill-defined. Here, we leveraged mouse models of viral cancer to simultaneous profile transcriptomic landscapes virus-specific tumor-specific cells at single-cell resolution. Through in-depth comparison antigen-specific across distinct disease settings, define uncharacterized clarify roles for molecular regulators heterogeneity. Comparison uniquely accessible regions along predicted factor activity uncover regulatory networks that both guide enforce novel established spanning memory, residency, exhaustion. Further, have functionally defined several transcriptional in controlling during cancer, including undescribed Runx3. Together, our findings heterogeneity trajectories acute infection, chronic cancer. We show can be enhance promising immunotherapy approaches. AAI Intersect Fellowship Program Computational Scientists Immunologists (2022-2023)