Evidence map›Paper›PMID 34731163›Full record

ArticlePloS one2021

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

Jeffrey R Haswell, Kaia Mattioli, Chiara Gerhardinger, Philipp G Maass, Daniel J Foster, Paola Peinado, Xiaofeng Wang, Pedro P Medina, John L Rinn, Frank J Slack

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 31 citations in OpenAlex.

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  12. CRISPRi screens identify the lncRNA,Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Article
  14. The Current Situation and Development Prospect of Whole-Genome Screening.International journal of molecular sciences · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 3 countries.

Jeffrey R HaswellDepartment of Pathology, HMS Initiative for RNA Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
Kaia MattioliDepartment of Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, United States of America.
Chiara GerhardingerDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, United States of America.
Philipp G MaassGenetics and Genome Biology Program, SickKids Research Institute, Toronto, Ontario, Canada.
Daniel J FosterDepartment of Pathology, HMS Initiative for RNA Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.ORCID 0000-0002-2466-9484
Paola PeinadoDepartment of Biochemistry and Molecular Biology, University of Granada, Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
Xiaofeng WangDepartment of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America.
Pedro P MedinaDepartment of Biochemistry and Molecular Biology, University of Granada, Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
John L RinnDepartment of Biochemistry, University of Colorado, BioFrontiers Institute, Boulder, Colorado, United States of America.
Frank J SlackDepartment of Pathology, HMS Initiative for RNA Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.ORCID 0000-0001-8263-0409
Beth Israel Deaconess Medical Center · USPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research · ESBroad Institute · USDartmouth College · USHarvard University · USUniversity of Colorado Boulder · USUniversity of Toronto · CA

Funding

Regulatory Roles and Dynamics of Nuclear long-noncoding RNAs in PluripotencyP01GM099117 · NIGMS · HARVARD UNIVERSITY · PI MEISSNER, ALEXANDER · 2011 to 2021
$21.2M
NIGMS NIH HHS P01 GM099117
6 · The paper itself

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.

Indexed as

Cell DifferentiationCRISPR-Cas SystemsForkhead Transcription FactorsHumansRNA InterferenceRNA, Long NoncodingForkhead Transcription FactorsFOXD3 protein, humanRNA, Long Noncoding

Identifiers

PMID34731163
PMCPMC8565776
OpenAlexW3211243880

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.