@misc{10481/73240,
year = {2021},
month = {11},
url = {http://hdl.handle.net/10481/73240},
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 developed a
clustering approach to infer mechanisms of action of lncRNA hits based on a variety of
genomic features. We subsequently identified and validated FOXD3-AS1 as a functional
lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and
methodology described herein can be adapted to discover and characterize novel regulators
of differentiation into any lineage.},
organization = {United States Department of Health & Human Services
National Institutes of Health (NIH) - USA	P01GM099117},
organization = {National Science Foundation (NSF)	DGE1144152},
publisher = {Public Library of Science},
title = {Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency},
doi = {10.1371/journal.pone.0252848},
author = {Haswell, Jeffrey R. and Peinado Fernández, Paola and Medina Vico, Pedro Pablo},
}