Evidence map›Paper›PMID 27229144›Full record

ArticleScience (New York, N.Y.)2016

Whole-organism lineage tracing by combinatorial and cumulative genome editing.

Aaron McKenna, Gregory M Findlay, James A Gagnon, Marshall S Horwitz, Alexander F Schier, Jay Shendure

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 454 papers.

0numbers the graph read from it
0cells of the map it votes in
454citing 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

454 citing papers in PubMed.

  1. Article
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  5. Review
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  7. Article
  8. Review
  9. Genomic repeats for single-cell molecular recording.bioRxiv : the preprint server for biology · 2026
    Article
  10. Article
  11. Article
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  13. Article
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  15. Review
  16. Article
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  19. Article
  20. Clonal dynamics deviate from neutral drift in zebrafish spermatogenesis.bioRxiv : the preprint server for biology · 2026
    Article

394 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Aaron McKennaDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Gregory M FindlayDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
James A GagnonDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Marshall S HorwitzDepartment of Genome Sciences, University of Washington, Seattle, WA, USA. Department of Pathology, University of Washington, Seattle, WA, USA.
Alexander F SchierDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA. Center for Brain Science, Harvard University, Cambridge, MA, USA. The Broad Institute of Harvard and MIT, Cambridge, MA, USA. FAS Center for Systems Biology, Harvard University, Cambridge, MA, USA. shendure@uw.edu schier@fas.harvard.edu.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA, USA. Howard Hughes Medical Institute, Seattle, WA, USA. shendure@uw.edu schier@fas.harvard.edu.

Funding

University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
EXPERIMENTAL PATHOLOGY OF CARDIOVASCULAR DISEASET32HL007312 · NHLBI · UNIVERSITY OF WASHINGTON · PI MAJESKY, MARK W., SCHWARTZ, STEPHEN MARK · 1985 to 2019
$11.8M
GENETIC MECHANISMS OF AXIS FORMATION IN VERTEBRATESR01GM056211 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SCHIER, ALEXANDER F · 1997 to 2015
$5.1M
Comprehensive Classification Of Neuronal Subtypes By Single Cell TranscriptomicsU01MH105960 · NIMH · HARVARD UNIVERSITY · PI REGEV, AVIV, SANES, JOSHUA R · 2014 to 2016
$4.5M
Interpreting Genetic Variants of Uncertain SignificanceDP1HG007811 · NHGRI · UNIVERSITY OF WASHINGTON · PI SHENDURE, JAY ASHOK · 2013 to 2017
$3.8M
Embryonic gene regulatory networks from spatially resolved transcriptomesR01HD085905 · NICHD · HARVARD UNIVERSITY · PI SCHIER, ALEXANDER F · 2016 to 2019
$2.6M
Genetic Mechanisms of Axis Formation in VertebratesR37GM056211 · NIGMS · HARVARD UNIVERSITY · PI SCHIER, ALEXANDER F · 2016 to 2019
$1.5M
Howard Hughes Medical InstituteNCCDPHP CDC HHS DP1HG007811NHGRI NIH HHS DP1 HG007811NHLBI NIH HHS T32 HL007312NHLBI NIH HHS T32HL007312NICHD NIH HHS HD085905NICHD NIH HHS R01 HD085905NIGMS NIH HHS GM056211NIGMS NIH HHS R01 GM056211NIGMS NIH HHS R37 GM056211NIGMS NIH HHS T32 GM007266NIMH NIH HHS MH105960NIMH NIH HHS U01 MH105960
6 · The paper itself

Abstract

Multicellular systems develop from single cells through distinct lineages. However, current lineage-tracing approaches scale poorly to whole, complex organisms. Here, we use genome editing to progressively introduce and accumulate diverse mutations in a DNA barcode over multiple rounds of cell division. The barcode, an array of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 target sites, marks cells and enables the elucidation of lineage relationships via the patterns of mutations shared between cells. In cell culture and zebrafish, we show that rates and patterns of editing are tunable and that thousands of lineage-informative barcode alleles can be generated. By sampling hundreds of thousands of cells from individual zebrafish, we find that most cells in adult organs derive from relatively few embryonic progenitors. In future analyses, genome editing of synthetic target arrays for lineage tracing (GESTALT) can be used to generate large-scale maps of cell lineage in multicellular systems for normal development and disease.

Indexed as

Bacterial ProteinsCell LineageCRISPR-Cas SystemsEndonucleasesAnimalsCell DivisionCell TrackingCRISPR-Associated Protein 9DNA Barcoding, TaxonomicGenetic EngineeringMutationSingle-Cell AnalysisStem CellsZebrafishZygoteBacterial ProteinsCas9 protein, Francisella novicidaCRISPR-Associated Protein 9Endonucleases

Identifiers

PMID27229144
PMCPMC4967023

What OpenQuestion holds

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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.