Evidence map›Paper›PMID 36917981›Full record

ArticleMolecular cell2023

Massively parallel characterization of CRISPR activator efficacy in human induced pluripotent stem cells and neurons.

Qianxin Wu, Junjing Wu, Kaiser Karim, Xi Chen, Tengyao Wang, Sho Iwama, Stefania Carobbio, Peter Keen, Antonio Vidal-Puig, Mark R Kotter and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 3% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
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  12. What makes genes burst.Trends in cell biology · 2026
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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

11 authors at 3 institutions in 3 countries.

Qianxin WuWellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. Electronic address: qw2@sanger.ac.uk.
Junjing WuWellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
Kaiser KarimDepartment of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.
Xi ChenWellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; Southern University of Science and Technology, 1088 Xueyuan Ave, Nanshan, Shenzhen, Guangdong 518055, China.
Tengyao WangDepartment of Statistics, London School of Economics and Political Science, London WC2B 4RR, UK.
Sho IwamaWellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Stefania CarobbioWellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; Metabolic Research Laboratories, Addenbrooke's Treatment Center, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK; Centro de Investigacion Principe Felipe, 46012 Valencia, Spain.
Peter KeenWellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Antonio Vidal-PuigWellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; Metabolic Research Laboratories, Addenbrooke's Treatment Center, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK; Centro de Investigacion Principe Felipe, 46012 Valencia, Spain.
Mark R KotterDepartment of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.
Andrew BassettWellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. Electronic address: ab42@sanger.ac.uk.
Wellcome Sanger Institute · GBUniversity of Cambridge · GBLondon School of Economics and Political Science · GB

Funding

Medical Research Council MC_UU_00014/2Medical Research Council MC_UU_00014/5Wellcome Trust
6 · The paper itself

Abstract

CRISPR activation (CRISPRa) is an important tool to perturb transcription, but its effectiveness varies between target genes. We employ human pluripotent stem cells with thousands of randomly integrated barcoded reporters to assess epigenetic features that influence CRISPRa efficacy. Basal expression levels are influenced by genomic context and dramatically change during differentiation to neurons. Gene activation by dCas9-VPR is successful in most genomic contexts, including developmentally repressed regions, and activation level is anti-correlated with basal gene expression, whereas dCas9-p300 is ineffective in stem cells. Certain chromatin states, such as bivalent chromatin, are particularly sensitive to dCas9-VPR, whereas constitutive heterochromatin is less responsive. We validate these rules at endogenous genes and show that activation of certain genes elicits a change in the stem cell transcriptome, sometimes showing features of differentiated cells. Our data provide rules to predict CRISPRa outcome and highlight its utility to screen for factors driving stem cell differentiation.

Indexed as

Induced Pluripotent Stem CellsChromatinClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsHumansNeuronsTranscriptional ActivationChromatinchromatinCRISPRaCRISPR activationepigenetichiPSCiNeuronsp300single cellstem cellsVPR

Identifiers

PMID36917981
PMCPMC10114495
OpenAlexW4324045883

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.