Evidence map›Paper›PMID 38724692›Full record

ArticleNature methods2024

Multiplex profiling of developmental cis-regulatory elements with quantitative single-cell expression reporters.

Jean-Benoît Lalanne, Samuel G Regalado, Silvia Domcke, Diego Calderon, Beth K Martin, Xiaoyi Li, Tony Li, Chase C Suiter, Choli Lee, Cole Trapnell and 1 more

Abstract read
In one paragraph

Article in Nature methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing 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

42 citing papers in PubMed.

  1. Review
  2. Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026
    Review
  3. bioRxiv : the preprint server for biology · 2026
    Article
  4. Locus-Scale Massively Parallel Reporter Assays.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  14. Article
  15. Article
  16. Scaling perturbations: beyond genome-scale CRISPR screens.bioRxiv : the preprint server for biology · 2026
    Article
  17. Article
  18. Review
  19. Article
  20. Review
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.

Jean-Benoît Lalanne *Department of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-8753-0669
Samuel G Regalado *Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Silvia DomckeDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Diego CalderonDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6990-9066
Beth K MartinDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9661-014X
Xiaoyi LiDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Tony LiDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Chase C SuiterDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Choli LeeDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-8901-1835
Cole TrapnellDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-8105-4347
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA, USA. shendure@uw.edu.ORCID http://orcid.org/0000-0002-1516-1865

Funding

CARDIOVASCULAR RESEARCH TRAINING PROGRAMT32HL007828 · NHLBI · UNIVERSITY OF WASHINGTON · PI Francis Kim, Farid Moussavi-Harami · 1997 to 2026
$10.2M
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
Versatile, exponentially scalable methods for single cell molecular profilingR01HG010632 · NHGRI · UNIVERSITY OF WASHINGTON · PI Jay Ashok Shendure, Bruce Colston Trapnell · 2019 to 2026
$5.9M
Optimization of a massively parallel genome editing approach to link regulatory elements to their target genes during mouse germ layer formationF31HG011576 · NHGRI · UNIVERSITY OF WASHINGTON · PI REGALADO, SAMUEL · 2021 to 2024
$208k
Characterizing the comprehensive gene regulatory basis of autoimmunity.F32HG011817 · NHGRI · UNIVERSITY OF WASHINGTON · PI CALDERON, DIEGO · 2021 to 2021
$64k
NHGRI NIH HHS F31 HG011576NHGRI NIH HHS F32 HG011817NHGRI NIH HHS R01 HG010632NHGRI NIH HHS UM1 HG011966NHLBI NIH HHS T32 HL007828U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) T32HL007828U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) F31HG011576U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) F32HG011817U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01HG010632U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1HG011966
6 · The paper itself

Abstract

The inability to scalably and precisely measure the activity of developmental cis-regulatory elements (CREs) in multicellular systems is a bottleneck in genomics. Here we develop a dual RNA cassette that decouples the detection and quantification tasks inherent to multiplex single-cell reporter assays. The resulting measurement of reporter expression is accurate over multiple orders of magnitude, with a precision approaching the limit set by Poisson counting noise. Together with RNA barcode stabilization via circularization, these scalable single-cell quantitative expression reporters provide high-contrast readouts, analogous to classic in situ assays but entirely from sequencing. Screening >200 regions of accessible chromatin in a multicellular in vitro model of early mammalian development, we identify 13 (8 previously uncharacterized) autonomous and cell-type-specific developmental CREs. We further demonstrate that chimeric CRE pairs generate cognate two-cell-type activity profiles and assess gain- and loss-of-function multicellular expression phenotypes from CRE variants with perturbed transcription factor binding sites. Single-cell quantitative expression reporters can be applied in developmental and multicellular systems to quantitatively characterize native, perturbed and synthetic CREs at scale, with high sensitivity and at single-cell resolution.

Indexed as

Gene Expression Regulation, DevelopmentalSingle-Cell AnalysisAnimalsChromatinGene Expression ProfilingGenes, ReporterHumansMiceRegulatory Elements, TranscriptionalRegulatory Sequences, Nucleic AcidTranscription FactorsChromatinTranscription Factors

Identifiers

PMID38724692
PMCPMC11166576

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.