Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states.

ABSTRACT: Cell atlas projects have nominated recurrent transcriptional states as drivers of biological processes and disease, but their origins, regulation, and properties remain unclear. To enable complementary functional studies, we developed a scalable approach for recapitulating cell states in vitro using CRISPR activation (CRISPRa) Perturb-seq. Aided by a novel multiplexing method, we activated 1,836 transcription factors in two cell types. Measuring 21,958 perturbations showed that CRISPRa activated targets within physiological ranges, that epigenetic features predicted activatable genes, and that the protospacer seed region drove an off-target effect. Perturbations recapitulated in vivo fibroblast states, including universal and inflammatory states, and identified KLF4 an

SUBMITTER: Southard KM 

PROVIDER: S-EPMC11312553 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature