Orthogonal CRISPR screens to identify transcriptional and epigenetic regulators of human CD8 T cell function.

ABSTRACT: The clinical response to adoptive T cell therapies is strongly associated with transcriptional and epigenetic state. Thus, technologies to discover regulators of T cell gene networks and their corresponding phenotypes have great potential to improve the efficacy of T cell therapies. We developed pooled CRISPR screening approaches with compact epigenome editors to systematically profile the effects of activation and repression of 120 transcription factors and epigenetic modifiers on human CD8+ T cell state. These screens nominated known and novel regulators of T cell phenotypes with BATF3 emerging as a high confidence gene in both screens. We found that BATF3 overexpression promoted specific features of memory T cells such as increased IL7R expression and glycolytic capacity, while attenuat

SUBMITTER: McCutcheon SR 

PROVIDER: S-EPMC10187198 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature