Evidence map›Paper›PMID 34115987›Full record

ArticleCancer cell2021

Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EMT states.

Kamen P Simeonov, China N Byrns, Megan L Clark, Robert J Norgard, Beth Martin, Ben Z Stanger, Jay Shendure, Aaron McKenna, Christopher J Lengner

Open access · bronzeAbstract read
In one paragraph

Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers.

0numbers the graph read from it
0cells of the map it votes in
244citing papers in PubMed
22.4field-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

244 citing papers in PubMed, 355 citations in OpenAlex.

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  12. Genomic repeats for single-cell molecular recording.bioRxiv : the preprint server for biology · 2026
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184 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 1 country.

Kamen P SimeonovMedical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: kamen.simeonov@gmail.com.
China N ByrnsMedical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
Megan L ClarkDepartment of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Robert J NorgardAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Beth MartinDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Ben Z StangerAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell & Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA, USA; Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA, USA. Electronic address: shendure@uw.edu.
Aaron McKennaDepartment of Molecular & Systems Biology, Dartmouth Geisel School of Medicine, Lebanon, NH, USA. Electronic address: aaron.mckenna@dartmouth.edu.
Christopher J LengnerDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell & Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: lengner@vet.upenn.edu.
University of Pennsylvania · USCancer Research Institute · USCalifornia Institute for Regenerative Medicine · USDartmouth College · USHoward Hughes Medical Institute · USUniversity of Washington · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
Graduate Training in Developmental BiologyT32HD083185 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Michael Granato, Foteini Mourkioti · 2015 to 2026
$4.0M
Deregulation of MSI RNA-binding proteins promotes intestinal tumorigenesisR01CA168654 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LENGNER, CHRISTOPHER JOACHIM · 2012 to 2021
$3.7M
VMD-PhD Training in Infectious Disease-Related ResearchT32AI070077 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Michael Lee Atchison · 2008 to 2026
$3.5M
Multidimensional cell recording with single-cell genomicsR00HG010152 · NHGRI · DARTMOUTH COLLEGE · PI MCKENNA, AARON H · 2019 to 2021
$729k
Phylogenetic reconstruction of the intestinal epithelium via evolving barcodesF30DK120135 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SIMEONOV, KAMEN P · 2018 to 2021
$106k
Howard Hughes Medical InstituteNCI NIH HHS P30 CA023108NCI NIH HHS R01 CA168654NHGRI NIH HHS R00 HG010152NIAID NIH HHS T32 AI070077NICHD NIH HHS T32 HD083185NIDDK NIH HHS F30 DK120135
6 · The paper itself

Abstract

The underpinnings of cancer metastasis remain poorly understood, in part due to a lack of tools for probing their emergence at high resolution. Here we present macsGESTALT, an inducible CRISPR-Cas9-based lineage recorder with highly efficient single-cell capture of both transcriptional and phylogenetic information. Applying macsGESTALT to a mouse model of metastatic pancreatic cancer, we recover ∼380,000 CRISPR target sites and reconstruct dissemination of ∼28,000 single cells across multiple metastatic sites. We find that cells occupy a continuum of epithelial-to-mesenchymal transition (EMT) states. Metastatic potential peaks in rare, late-hybrid EMT states, which are aggressively selected from a predominately epithelial ancestral pool. The gene signatures of these late-hybrid EMT states are predictive of reduced survival in both human pancreatic and lung cancer patients, highlighting their relevance to clinical disease progression. Finally, we observe evidence for in vivo propagation of S100 family gene expression across clonally distinct metastatic subpopulations.

Indexed as

Epithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticAnimalsCell LineageCell Line, TumorCell ProliferationCRISPR-Cas SystemsHumansMaleMiceMice, Inbred NODPancreatic NeoplasmsS100 ProteinsSequence Analysis, RNASingle-Cell AnalysisStem CellsS100 ProteinsbarcodingCRISPREMTepithelial-to-mesenchymal transitionevolving barcodeslineage tracingmetastasisphylogeneticsS100single cell

Identifiers

PMID34115987
PMCPMC8782207
OpenAlexW3169899682

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.