Evidence map›Paper›PMID 36635387›Full record

ArticleNature genetics2023

A single-cell massively parallel reporter assay detects cell-type-specific gene regulation.

Siqi Zhao, Clarice K Y Hong, Connie A Myers, David M Granas, Michael A White, Joseph C Corbo, Barak A Cohen

Open access · greenAbstract read
In one paragraph

Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
12.3field-weighted citation impact, top 1% 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

57 citing papers in PubMed, 80 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. aBIOTECH · 2025
    Review
  13. Review
  14. Context-dependent regulatory variants in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Combining Machine Learning and Multiplexed,bioRxiv : the preprint server for biology · 2025
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Siqi ZhaoEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine, St. Louis, MO, USA.
Clarice K Y HongEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9485-1425
Connie A MyersDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
David M GranasEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine, St. Louis, MO, USA.
Michael A WhiteEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-8511-6026
Joseph C CorboDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Barak A CohenEdison Family Center for Systems Biology and Genome Sciences, Washington University School of Medicine, St. Louis, MO, USA. cohen@wustl.edu.ORCID http://orcid.org/0000-0002-3350-2715
Washington University in St. Louis · US

Funding

PROMOTERSR01GM092910 · NIGMS · WASHINGTON UNIVERSITY · PI Barak A Cohen · 2011 to 2026
$6.6M
Elucidating the cis-regulatory grammar of human photoreceptorsR01EY030075 · NEI · WASHINGTON UNIVERSITY · PI CORBO, JOSEPH · 2020 to 2023
$2.2M
High-throughput analysis of the effects of gene promoters and chromosomal environments on single-cell gene expressionR01HG012304 · NHGRI · WASHINGTON UNIVERSITY · PI COHEN, BARAK A · 2022 to 2025
$1.7M
Molecular Properties of Transcription Factors that Control Cell-to-Cell Variability in Gene ExpressionR01GM140711 · NIGMS · WASHINGTON UNIVERSITY · PI COHEN, BARAK A · 2021 to 2024
$1.3M
NEI NIH HHS R01 EY030075NHGRI NIH HHS R01 HG012304NIGMS NIH HHS R01 GM092910NIGMS NIH HHS R01 GM140711
6 · The paper itself

Abstract

Massively parallel reporter gene assays are key tools in regulatory genomics but cannot be used to identify cell-type-specific regulatory elements without performing assays serially across different cell types. To address this problem, we developed a single-cell massively parallel reporter assay (scMPRA) to measure the activity of libraries of cis-regulatory sequences (CRSs) across multiple cell types simultaneously. We assayed a library of core promoters in a mixture of HEK293 and K562 cells and showed that scMPRA is a reproducible, highly parallel, single-cell reporter gene assay that detects cell-type-specific cis-regulatory activity. We then measured a library of promoter variants across multiple cell types in live mouse retinas and showed that subtle genetic variants can produce cell-type-specific effects on cis-regulatory activity. We anticipate that scMPRA will be widely applicable for studying the role of CRSs across diverse cell types.

Indexed as

Genes, ReporterHEK293 CellsAnimalsGene LibraryHumansMicePromoter Regions, GeneticRetina

Identifiers

PMID36635387
PMCPMC9931678
OpenAlexW4315779271

What OpenQuestion holds

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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.