Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency.

ABSTRACT: Although many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we devel

SUBMITTER: Haswell JR 

PROVIDER: S-EPMC8565776 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature