Evidence map›Paper›PMID 39294132›Full record

ArticleNature communications2024

Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements.

Florence M Chardon, Troy A McDiarmid, Nicholas F Page, Riza M Daza, Beth K Martin, Silvia Domcke, Samuel G Regalado, Jean-Benoît Lalanne, Diego Calderon, Xiaoyi Li and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
–field-weighted citation impact
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

41 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Crosstalk BetweenCancers · 2026
    Review
  5. Article
  6. Review
  7. Article
  8. Frontiers in cell and developmental biology · 2026
    Article
  9. Review
  10. Review
  11. Article
  12. Large-scale discovery of neural enhancers for cis-regulation therapies.bioRxiv : the preprint server for biology · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Florence M Chardon *Department of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID 0000-0001-8858-989X
Troy A McDiarmid *Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Nicholas F PageDepartment of Psychiatry and Behavioral Sciences, Kavli Institute for Fundamental Neuroscience, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Riza M DazaDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID 0000-0003-1635-8675
Beth K MartinDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Silvia DomckeDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Samuel G RegaladoDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Jean-Benoît LalanneDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Diego CalderonDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID 0000-0002-6990-9066
Xiaoyi LiDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Lea M StaritaDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID 0000-0003-2870-5099
Stephan J SandersDepartment of Psychiatry and Behavioral Sciences, Kavli Institute for Fundamental Neuroscience, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Nadav AhituvDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA. Nadav.Ahituv@ucsf.edu.ORCID 0000-0002-7434-8144
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA, USA. shendure@uw.edu.ORCID 0000-0002-1516-1865

Funding

Massively parallel characterization of variants and elements impacting transcriptional regulation in dynamic cellular systemsUM1HG011966 · NHGRI · UNIVERSITY OF WASHINGTON · PI Nadav Ahituv, Jay Ashok Shendure · 2021 to 2026
$9.7M
HIGHLY PARALLEL ANALYSIS OF 5' AND 3' UTR VARIANTS IN NEURODEVELOPMENTAL DISORDERSR01MH116999 · NIMH · WASHINGTON UNIVERSITY · PI JOSEPH D DOUGHERTY · 2018 to 2026
$5.1M
2/2 - Identification and Validation of Expression Quantitative Trait Loci (eQTLs) in discrete cell types across human brain developmentU01MH122681 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SANDERS, STEPHAN · 2021 to 2022
$1.2M
Characterizing the comprehensive gene regulatory basis of autoimmunity.F32HG011817 · NHGRI · UNIVERSITY OF WASHINGTON · PI CALDERON, DIEGO · 2021 to 2021
$64k
NHGRI NIH HHS F32 HG011817NHGRI NIH HHS UM1 HG011966NIMH NIH HHS R01 MH116999NIMH NIH HHS U01 MH122681U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1HG011966
6 · The paper itself

Abstract

CRISPR-based gene activation (CRISPRa) is a strategy for upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive cis-regulatory elements and the gene(s) they regulate. Random combinations of many gRNAs are introduced to each of many cells, which are then profiled and partitioned into test and control groups to test for effect(s) of CRISPRa perturbations of both enhancers and promoters on the expression of neighboring genes. Applying this method to a library of 493 gRNAs targeting candidate cis-regulatory elements in both K562 cells and iPSC-derived excitatory neurons, we identify gRNAs capable of specifically upregulating intended target genes and no other neighboring genes within 1 Mb, including gRNAs yielding upregulation of six autism spectrum disorder (ASD) and neurodevelopmental disorder (NDD) risk genes in neurons. A consistent pattern is that the responsiveness of individual enhancers to CRISPRa is restricted by cell type, implying a dependency on either chromatin landscape and/or additional trans-acting factors for successful gene activation. The approach outlined here may facilitate large-scale screens for gRNAs that activate genes in a cell type-specific manner.

Indexed as

CRISPR-Cas SystemsEnhancer Elements, GeneticSingle-Cell AnalysisAutism Spectrum DisorderClustered Regularly Interspaced Short Palindromic RepeatsHumansInduced Pluripotent Stem CellsK562 CellsNeuronsPromoter Regions, GeneticRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39294132
PMCPMC11411074

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Registered trials

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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.